Compositions and methods for treating ocular diseases
Patent Information
- Application Number
- AU2025282157
- Authority / Receiving Office
- AU · AU
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2024-06-06
- Filing Date
- 2025-06-04
- Publication Date
- 2026-10-22
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Abstract
Description
TECHNICAL FIELD
[0001] The present disclosure relates to a travoprost sustained release biodegradable intracameral implant 5 comprising a biodegradable hydrogel and travoprost particles. The present disclosure also relates to travoprost particles, optionally obtained by or obtaintabte by a process comprising a membrane emulsification step. The present disclosure also relates to a method of manufacturing travoprost particles, optionaliy wherein the method comprises a membrane emulsification step. The present disclosure also relates to a method of manufacturing a travoprost sustained release biodegradable intracameral implant. The present disclosure also relates to a method of treating an 10 ocular disease, such as glaucoma or ocular hypertension, comprising administering the travoprost particles or inserting the intracameral implant of the present disclosure into an eye of a subject in need of treatment. BACKGROUND OF THE DISCLOSURE
[0002] Glaucoma is typically a progressive, chronic disease affecting millions of people (Simmons, $., T. 15 Ophthalmic Formulations. Glaucoma Today Supplement to Advanced Ocular Care, 2010; The Eye Disease Prevalence Group., Prevalence of open-angle glaucoma among adults tn the United States. Arch Ophthalmol, 2004.122: p, 532538). In fact, glaucoma has been reported to be one of the leading causes of irreversible blindness, and worldwide it is the second leading cause of blindness (Quigley, H.A. and A.T. Broman, The number of people with glaucoma worldwide in 2010 and 2020. Sr J Ophthalmol, 2006. 90(3): p. 262-7). Some have projected that by the year 2040 20 mere than 110 million people would be diagnosed with glaucoma (Tham, Y.-C., et al., Global Prevalence of Glaucoma and Projections of Glaucoma Burden through 2040. B Ophthalmology, 2014. 121(11): p. 2081-2090).
[0003] Glaucoma is defined as optic neuropathy leading to the loss of retinal ganglion cells and their axons and progressing in later stages to toss of visual field and, in very advanced cases, central visual acuity, open-angle glaucoma is the most common form of the disease and primary' open angle, glaucoma (POAG) refers to eyes with 25 open anterior drainage angles and elevated intraocular pressure (IOP).
[0004] Elevated fluid pressure within the eye (Le, elevated intraocular pressure (IOP)), defined as pressures above the normal range of 10 to 21 mmHg, is the main risk factor for glaucoma. People with elevated IOP levels without any current optic-nerve damage are diagnosed with ocular hypertension, as opposed to glaucoma. However, people with ocular hypertension may be at risk of progressive damage to the optie nerve (glaucoma). 30
[0005] For bote glaucoma and ocular hypertension (OHT), the most critical factor for effective therapy is to lower the IOP, and in doing so, the disease progression may be slowed along with the rate of visual field loss. Drugs that are classified as prostaglandins have been shown to effectively lower 10P (AAO, Glaucoma Preferred Practice Pattern. 2015). The Preferred Practice Patterns of the AAO recommend prostaglandins as the first line of therapy far POAG and OHT. The most commonly prescribed topical medications for the treatment of glaucoma in the United States are the prostaglandin analogues. 5
[8006] Travoprost is an example of a suitable synthetic prostaglandin F2«. analogue, Its chemical name is (isopropyl (2)-7- [(lR,2Rf3R,5S)-3,5-dihydraxy-2-[(iEf3R)-3-hydroxy-4-[(a,a;a-trlffaoro-m~isopra^ butertyl]-cyclopentyl}-5-hepteno^ This procirag is a synthetic prostaglandin analogue that is enzymatically converted to a free acid form in human cornea (AMazzaf, AM., L. DeSantis, and P.A. Zetland, Travoprost: a patent ocular hypotensive agent. Drugs Today (Bare), 2003, 39(1); p. 61-74). Travoprost free acid like all prostaglandins Is 10 a selective FP prostanoid receptor agonist which is believed to reduce intraocular pressure by increasing trabecular meshwork and uveoscferal outflow (Um, K.S., et al., Mechanism of action of bimatoprast, latanoprast, and travoprost In healthy subjects. A crossover study. Ophthalmology, 2006. 115(5); p. 790-795 e4 and Torts, C.B., BAT. Gabeit, and P.L. Kaufman, Update on the Mechanism of Action of Topical Prostaglandins for Intraocular Pressure Reduction. Survey of Ophthalmology, 2008. 53(6,. Supplement): p. S107-S120), 15
[0007] Travoprost is the active ingredient in Travatan®, Travatan Z®, and Izba”* (al! Alcon Laboratories, Inc., Ft Worth, TX), which are all topical ophthalmic solations Intended to reduce elevated IOP. The dosage is typically one drop daily of a 0.004% or 0.003% solution applied daily to the affected eyefs).
[0008] Successful treatment: for glaucoma with available approved products requires daily seif-adminlstered treatment with topical eye drops. While topical antihypertensive medication may be effective in treating 20 glaucoma, any one of the available therapies wHl only be as effective as the adherence to administration by individual patients. Known limitations associated with the application of topical eye drops include; (1) difficulty in administering drops, (2) limited accuracy of drops getting into the eye, (3) potential washout of drops by lacrimation or subsequent administration of other drops, (4) the need for a caregiver to administer drops and (5) poor subject compliance (Toris, C.B., BAT. Gabeit, and P.L. Kaufman, Update on the Mechanism of Action of Topical Prostaglandins for 25 Intraocular Pressure Reduction. Survey of Ophthalmology, 2008. 53(6, Supplement)* p. S107-S120). Kholdebann, et al (Kholdebarin, R., et al.. Multicenter study of compliance and drop administration in glaucoma. Can J Ophthalmol, 2008. 43(4): p. 454-61) reported that 34% of patients used improper administration technique. For some patients there is the need to administer multiple drops, and this may complicate the situation due to washout effects. In one study, nearly 9% of the patients who required more than one medication In the same eye failed to wait at least three 30 minutes between administrations. Importantly, regardless of the number of medications, patients are expected to remain on treatment indefinitely and motivation to do so plays an important role, Accordingly, there is a need to provide an alternative to the dally administration of single or multiple eye drops for the treatment of glaucoma, especially in an aging population with the disease,
[6009] The risk of potential blindness as a long-term effect increases in cases of poorly managed 35 glaucoma, and patient compliance becomes an Important issue. Studies have shown that less than 50% of glaucoma patients continue therapy and refill prescriptions as required (Friedman, D.S., at ak, Using Pharmacy Claims Data to Study Adherence to Glaucoma Medications: Methodology and Findings of the Glaucoma Adherence and Persistency Study (GAPS). Investigative Ophthalmology & Visual Science, 2007. 48(11): p, 5052-5057), and most patients are likely to discontinue use of a topical therapy within 1.2 years after filling their first prescription according to health 5 insurance claims (Nordstrom, S,L, et al.. Persistence and Adherence With Topical Glaucoma Therapy. American Journal of Ophthalmology, 2005.140(4): p. 598.el-598.ell). Thus, a delivery system that would provide tang-term, 24 hour control of IGF could address a multitude of issues and potentially delay or prevent loss of vision resulting from glaucoma for a patient. [OOO1O] Ultimate goals of drug delivery to the anterior segment include improving patient compliance, 10 achieving an excellent safety profile and providing for sustained delivery over an extended period of time (Yeliepeddi, V.K. and S, Palakurthi, Recent Advances in Topical Ocular Drug Delivery, Journal of Ocular Pharmacology and Therapeutics, 2015. 32(2): p. 67-82), [OOOli] DURYSTA®, a bimatoprost intracamerai implant approved by the FDA, is indicated for the reduction, of intraocular pressure to patients with open angle glaucoma or ocular hypertension. The implant is limited to a single 15 implant per eye without retreatment due to possible corneal endothelial cell loss and corneal adverse reactions and should be used with caution in patients with narrow angles or anatomical angle obstructions. Efficacy was evaluated in two multicenter, randomized, paraHei-group, controlled 20-month (including 8-month extended follow-up) studies of DURYSTA compared to twice daily topical timolol 0.5% drops, in patients with open angel glaucoma or ocular hypertension. DURYSTA demonstrated an intraocular pressure reduction of approximately 5-8 mmHg in patients with 20 a mean baseline intraocular pressure of 24.5 mmHg. The data show a raise in intraocular pressure for the DURYSTA group above the timolol group after week 12. DURYSTA^ is an intracameral implant containing 10 pg of bimatoprost, in a solid polymer sustained-retea.se drug delivery system. The drug delivery system consists of poly (D,L-iattMe), poly (D,l-!adide-co-glycoiide), poly (D.L-acfide) acid end, and polyethylene glycol 3350. Reference is made to the DURYSTA prescribing information. 25 SUMMARY OF THE DISCLOSURE
[00012] In one aspect, the present disclosure is directed to a travoprost sustained release biodegradable intracameral implant comprising a biodegradable hydrogel and travoprost particles, wherein the biodegradable hydrogel comprises a polymer network comprising one or more units Of polyalkytene 30 glycol, wherein the travoprost particles are a mixture of travoprost and a biodegradable polymer, wherein the travoprost particles are dispersed within the biodegradable hydrogel, and wherein the travoprost particles have a median diameter of about 2 pm to about 19 pm as determined by laser diffraction.
[00013] In another aspect, the present disclosure is directed to a kit comprising an intracameral implant of the present disclosure and an injection device for intracameral injection of the intracameral implant.
[00014] in yet another aspect, the present disclosure is directed to a syringe for intracameral injection, wherein the syringe is loaded with an intracameral implant according to the present disclosure. 5
[00015] In yet another aspect, the present disclosure is directed to travoprost partides, wherein the travoprost particles are a mixture of travoprost and a biodegradable polymer and wherein the travoprost particles have a median diameter of about 2 pm to about 19 pm as determined by laser diffraction. In some embodiments, the travoprost particles are obtained by or are obtainable by a process comprising a membrane emulsification step.
[00016] In yet another aspect, toe present disclosure is directed to a method of manufacturing travoprost 10 particles, wherein the travoprost particles are a mixture of travoprost and a biodegradable polymer and wherein the method comprises a membrane emulsification step.
[00017] in yet another aspect, the present disclosure is directed to a method of manufacturing a travoprost sustained release biodegradable intracameral implant, wherein the implant comprises the travoprost particles of the present disclosure. In some embodiments, the present disclosure is directed to a method of manufacturing a 15 travoprost sustained release biodegradable intracameral implant, the method comprising: -preparing or providing travoprost particles of the present disclosure, -preparing a precursor mixture of an electrophilic nroup-containing multi-arm polyethylene glycol precursor and the travoprost particles, -crosslinking the precursor mixture using a nucleophilic group-containing crosslinking agent to form a polymer 20 network, thereby obtaining a biodegradable hydrogel comprising toe polymer network, wherein the travoprost partictes are dispersed in the biodegradable hydrogel, and -drying the biodegradable hydrogel to provide the implant.
[00018] In yet another aspect, the present disclosure is directed to a method of treating an ocular disease in a subject in need thereof comprising inserting an intracameral implant of the present disclosure into an eye of the 25 subject in need of treatment or comprising administering travoprost particles of the present disclosure into an eye of the subject in need of treatment. In some embodiments, the ocular disease is glaucoma, such as open angle glaucoma. In some embodiments, the ocular disease is ocular hypertension. In some embodiments, the subject is a human. Said methods of the present disclosure have the potential for preservative free treatment of human subjects.
[00019] In yet another aspect, the present disclosure Is directed to a method of redoing the intraocular 30 pressure in a subject with ocular hypertension or glaucoma, such as open angle glaucoma, comprising inserting an intracameral Implant of the present disctosure into an eye of the subject in need of treatment or comprising administering travoprost particles of the present disclosure into an eye of the subject in need of treatment. In some embodiments, the subject is a human. Said methods of the present disclosure have the potential for preservative free treatment of human subjects.
[00020] in some aspects, the present: disclosure is also directed to microparticles with alternative active ingredients than travoprost, such as other prostaglandin analogues. Examples of other prostaglandin analogues are 5 Iatanoprost, tafluprost, bimatoprost, unoprostone, unoprostone isopropyl ester, and latanoprostene bunod. In some embodiments, the present disclosure is thus also directed to bimatoprost particles, wherein the bimatoprost particles are a mixture of bimatoprost and a biodegradable polymer and wherein the bimatoprost particles have a median diameter of about 2 pm to about 19 pm as determined by laser diffraction. In some embodiments, the present disclosure is thus also directed to tafluprostparticles, wherein the tafluprost particles are a mixture of tafluprost and 10 a biodegradable polymer and wherein the tafluprost particles have a median diameter of about 2 pm to about 19 pm as determined by laser diffraction. In some embodiments, the present disclosure is thus also directed to iatanoprost partides, wherein the Iatanoprost particles are a mixture of Iatanoprost and a biodegradable polymer and wherein the iatanoprost particles have a median diameter of about 2 pm to about 19 pm as determined by laser diffraction. In some aspects, the present disclosure is thus also directed to corresponding sustained release biodegradable 15 intracameral implants comprising a biodegradable hydrogel and such alternative prostanglandin analogue particles, including bimatoprost particles, tafluprost particles, or Iatanoprost particles.
[00021] The travoprost particles according to certain aspects of the present disclosure show a comparably small median particle diameter (see, for instance, also the experimental data in Example i), When applied in travoprost sustained release intracameral implants, said travoprost particles according to the present disclosure 20 provide for a desirable release profile of travoprost, which is, in some embodiments close to linear release and / or zero-order reiease when measured to vitra In some embodiments, the intracamera! implant comprising said travoprost particles according to the present discosure provides for a close to linear release and / or zero-order release of travoprost when meassured to wtefor an extended period of time, such as for about 1 month, about 1.5 months, about 2 months, about 2.5 months, about 3 months, about 3.5 months, or about 4 months. In some embodiments, 25 the intracameral Implants of the present disclosure only show a limited burst at the beginning of the to t-ste? release measurements (such as a burst of below about 20% at Day 1), See, for instance, also the experimental data in Examples 2 and 3.
[00022] Surpdsingiiy, the desirable release profile of travoprost when measured under to vitro 'Conditions can be obtained with an Intracameral implant comprising only one single travorpost particle type (in some 30 embodiments, the one single travoprost partide type contains a biodegradable polymer, such as a polylactide, having a specific inherent viscosity). In embodiments where only a single bavoprost particle type is applied per implant (compared to a blend of different travoprost particle types), the manufacturing process is simplified (e.g, a step of mixing of different travoprost particle types is not required), and costs are thus safed, Also, the use of only a single travoprost particle type may yield a more uniform final implant product, for instance, also the experimental data 35 in Examples 2 and 3.
[00023] Smaller particles may be beneficial due to properties such as flow kinetics within the hydrogel precursor solution and / or toe increased total number of micropartides per unit volume, creating a simpler and more straightforward process to fabricate into implants, which may yield a more uniform finat product with a comparable release profile than implants with different particle types containing a larger particle diameter. Additionally, due to 5 the improved packaing efficiency of smaller particles, implants of comparably narrow diameter compared to Implants with a blend of larger particles can be provided, while maintaining the same dose and a similar drug release profile. See, for example, also the experimental data in Examples 1 to 3.
[00024] The travoprost particle manufacturing process according to the present disclosure comprising a membrane emulsification step provides for a high partide yield (in some embodiments, yields of over 70%}. 10 Moreover, uniform particles can be produced. As shown herein (reference is made in particular to Example 1), membrane emulsification allows for a narrow particle size distribution as well as the capability to fabricate microparticles of smaller diameter in higher yield than possible by other microparticle production processes, such as homogenization. Moreover, the travoprost-ioaded microparticles produced by the method of the present disclosure have a smooth and spherical morphology (see also toe SEM images referred to in Example 1), Also for producing I 5 comparably larger particle size diameters (such as about 20 to about 55 pm average particle size diameter) membrane emulsification is applicable. To prepare such comparably larger particle size diameters, membrane emulsification does not require a subsequent step of sieving, compared to other microparticle production processes, such as homogenization. [00G25] The various aspects and embodiments of the present disclosure are further described herein, in 20 particular, in the detailed description below. BRIEF DESCRIPTION OF THE DRAWINGS [GQG26] Figure 1 Schematic overview of travoprost particle production process including a membrane emulsification step (process flow diagram including AXF-Mini). 25
[00927] Figure 2 Schematic overview of microparticles with PLA and travoprost:,
[00028] Figure 3 Particle size distribution <PSD) of travoprost; loaded PLA microparticles produced with 4A PLA as measured by laser diffraction (AXF-MW),
[00029] Figure 4A Scanning electron microscopy (SEM) images of travoprost:-loaded PLA micropartides produced with 4A PLA (AXF-Mini), 30
[00030] Figure 4B SEM images of implants containing only one single type of travoprost-loaded PLA microparticles produced with 4A PLA (AXF-Mini). Implants are shown from end and side view.
[00031] Figure 5 PSD of tevaprosMoadod PLA microparticles produced with 7A PLA as measured by laser diffraction (AXF-Mml).
[00032] Figure 6A SEM images of travoprost-loaded PLA micropartides produced with 7A PLA (AXF-Mini).
[00033] Figure 68 SEM Images of implants containing only one single type of travoprost-loaded PLA microparticles produced with 7A PLA (AXF-Mini). Implants are shown from end and side view..
[00034] Figure 7 PSD of travoprost-ioaded PLA microparticles produced with 9A PLA as measured by laser diffraction (AXF-Mini).
[00035] Figure SA SEM images of fravoprost-toaded PLA microparticles produced with 9A PLA (AXF-Mini).
[00036] Figure. 88 SEM images of implants containing only one single type of travoprost-loaded PLA microparticles produced with 9A PLA (AXF-Mini). Implants are shown from end and side view.
[00037] laser diffr actj< Figure 9 PSD of travoprost-loaded PLA microparticles produced with 5.5E PLA. as measured by jn (AXF-Mini).
[00038] Figure ISA SEM images of travoprost-loaded PLA microparticles produced with 5.5E PLA (AXF- [OO039] Figure 208 SEM images of implants containing only one single type of travoprost-loaded PLA microparticles produced with 5.5E PLA. (AXF-Minl). Implants are shown from end and side view.
[00040] Figure XI PSD of travoprast'lgaded PLA microparticles produced with 4A PLA as measured by laser diffraction (LDC1).
[00041] Figure 12 PSD of travoprost-loaded PLA microparticles produced with 9A PLA as measured by laser diffraction (LDC-1).
[00042] Figure 13 PSD of travoprost-loaded PLA microparticles produced with 5.5E PLA as measured by laser diffraction (LDC1).
[00043] Figure 14 In travoprost release at 37°C from implants containing only one single type, of travoprost-loaded PLA microparticles produced with 4A, 7A, 9A, or 5.SE PLA, respectively (produced with AXF-Mini; D50 of the particles is about 8 to 9 pm; see also Figures 3 to 20), Release media was lx PBS with Q.5% PEG-40 hydrogenated castor oil and 0,.81% sodium fluoride. The spike at Day 7 is attributed to a sampling error. [O0O44] Figure 15 Zr? wfrotravoprast release at 37°C from Implants containing only one single type of travoprost-loaded PLA microparticles produced with 4A, 9A, or 5.5E PLA, respectively (produced with LDC-1; 050 of the partides is about 10 to 13 pm; see also Figures 11 to 13). Release media was lx PBS with 0.5% PEG-40 hydrogenated castor oil and 0.01% sodium flucride. (00045) Figure 10 In wfrotravoprost release at 40*0 from implants containing only one single type of travoprest-loaded RA microparticles produced with 4A, 9A, or 5.5E PLA, respectively (produced with LDC-1; D50 of the particles is about 10 to 13 pm; see also Figures 11 to 13). Release media was lx PBS with 0.5% PEG-40 hydrogenated castor oil and 0.01 % sodium fluoride.
[00046] Figure 17 In wte? travoprost release at 37SC from implants containing one single type of travoprost-loaded PLA microparticles produced with 4A or a blend of different types of travoprost-loaded PLA microparticles produced with 4A and 7A; 4A, 7 A, and 9A; and 4A, 7A, 9A, and 5.5E PLA (average partide size is about 20 to 53 pm as measured by sieving). Release media was lx PBS with 0,5% PEG-40 hydrogenated castor oil and 0.01% sodium fluoride. All release profiles are normalized to 100% release.
[00047] Figure 13 Syringe assembly suitable for administering an implant of the present disclosure, DEFINITIONS [00048) Some terms and expressions used in the present disclosure are defined in the following chapter ("Definitions"). However, further definitions might be found throughout the entire disclosure.
[00049] Ail documents cited and referred to herein are herewith incorporated by reference in their entirety.
[00050] As used herein, the term '"about* in connection with a number, refers to the number recited thereafter and numbers within 10% above or below of said recited number. For example, the term "about 15,000 Da" means "15,000 ± 10%", If the term "about" is used prior to a percentage, the term about cannot modify the percentage above a value of 100%. For example, the term "about 95%* refers to a range of 85.5% to 100%. If the number following the term “about” refers to a parameter and the present disclosure provides for a measurement method of said parameter, the term "about” refers to the measurement error of said measurement method as expected by one of ordinary skill In the art when making the measurement and exercising a level of care commensurate with the objective of measurement and toe precision of the measuring equipment.
[00051] As used herein, the singular forms "a," "an," and "the" include plural references unless the context clearly indicates otherwise.
[90052] The term ’’and / or" as used in a phrase such as "A and / or B" herein is intended to include both "A and B” and "A or B".
[90053] Open terms such as "include," ’'including," ’’contain," "containing" and the like mean "comprising." These open-ended transitional phrases are used to introduce an open-ended list of elements, method steps, or the like that does not exclude additional, unrecited elements or method steps.
[00054] The term "consisting of" is a closed term. This closed-ended transitional phrase means that no 5 further elements, method steps, or the like that are not recited can be present.
[00055] The term "consisting essentially of" means that further, unrecited elements, method steps, or the like can be present, namely those not materially affecting the essential characteristics of the described method, product, use, or the like.
[00058] The term 'intracamerai implant" as used herein (might also be referred to as " intracamerai insert") 10 refers to an object that contains travoprost and that is suitable to be inserted to the anterior chamber of an eye, in particular, to the anterior chamber of a human eye. The intracamerai implant can remain in toe anterior chamber of an eye tor a certain period of time, white it releases the active agent (travoprost) into the surrounding environment, in particular Inta the aqueous humor. In some embodiments, the intracamerai Implant is in the form of a fiber in Its dried state. The shape of the implant in its dried state may be maintained to a-certain degree upon placing the 15 implant into a subject's eye, although dimensions of the implant (e.g. length and / or diameter) may change after administration due to hydration in the subject's eye. The implant is completely formed prior to being administered; in other words, what is inserted into the eye is not a solution or suspension, but an already shaped, defined object. An intracamerai implant can be designed to be biodegradable over the course of time and thus may thereby soften, change its shape and / or decrease In size, and ultimately might be eliminated / blodegraded either by complete 20 dissolution or disintegration. In the present disclosure the term "Implant" is used to refer bath to an Implant in a hydrated (also called "swollen") state when it contains water (e.g. after the implant has been (re-)hyd rated once: administered to the eye or otherwise immersed into an aqueous environment) and to an implant: In Its dry (dried / dehydrated) state, e,g., when it has been dried to a low water content of e.g. not more than 1% by weight or when the preparation results In a low water content Insert without the necessity of a drying step. The water content 25 of the implant can be measured using a Karl Fischer coulometric method, such as shown in Example 5 below. [0QQ57] The term "Inserted" is interchangeably used herein with the terms "placed" or ''Injected'' or "administered" or "implanted". For example, an intracamerai implant according to the present disclosure may be "inserted" (or, alternatively, "injected") into the eye of a subject. Insertion can occur into only one of the subject's eyes or into both of the subject’s eyes (bilateral). 30 [0G058] The term "ocular" as used in the present disclosure refers to the eye in general, or any part or portion of the eye (as an "ocular implant" can in principle be administered to any part or portion of the eye).
[00059] The term "b-odegradafte" refers to a material or object (such as the intracamerai implant according to the present disclosure) which becomes degraded in wrty i.e., when placed in the human body. In the context of certain embodiments of the present disclosure, as disclosed in detail herein below, the implant comprising the hydrogel within which the active ingredient is contained, slowly biodegrades over time once administered into the anterior chamber of the eye, In certain embodiments, biodegradation takes place at least In part via ester hydrolysis in the aqueous environment of the anterior chamber of the eye. The Implant slowly softens and disintegrates, resulting in clearance through the liquefying and clearing through aqueous humor outflow pathways.
[00060] A "hydrogel" is a three-dimensional network of one or more hydrophilic natural or synthetic polymers (as disclosed herein) that can swell in water and hold an amount of water white maintaining or substantially maintaining its structure, e,g,, due to chemical or physical cross-linking of individual polymer chains. Due to their high-water content, hydrogels are soft and flexible, which make them similar to natural tissue. In the present disclosure, the term “hydrogel" is used to refer both to a hydrogel in the hydrated state when ft contains water (e.g. after the hydrogel has been formed In an aqueous solution, or after the hydrogel has been hydrated or (re-)hydrated once inserted into the eye or otherwise immersed into an aqueous environment) and to a hydrogel in its dry (dried / dehydrated) state, e.g., when it has been dried to a low water content of e.g. not more than 1% by weight or when the preparation results in a low water content insert without the necessity of a drying step. In the present disclosure, wherein an active principle is contained (e,g, dispersed) in a hydrogel, the hydrogel may also be referred to as a "matrix".
[00081] The term "polymer network” describes a structure formed of polymer chains (of the same or different molecular structure and of the same or different molecular weight) that are cross-linked with each other, The types of polymers suitable for the purposes of the present disclosure are disclosed herein below. The polymer network may be obtained by reacting an electrophilic group-containing muitl-arm-polymer precursor with a nucleophilic group-containing cross-linking agent.
[00062] The term “fiber" as disclosed herein refers to a shape that is essentially cylindrical and characterized by a diameter and a length.
[00063] The term "amorphous" refers to a polymer or polymer network, which does not exhibit crystalline structures in X-ray or electron scattering experiments.
[00064] The term "semi-crystalline" refers to a polymer or polymer network, which possess® some crystalline character, i.e., exhibits some crystalline properties in X-ray or electron scattering experiments.
[00065] As used herein, ’’homogenously dispersed" (briefly also referred to herein as "dispersed") means that the travoprost particles are uniformly dispersed throughout the hydrogel or polymer network.
[00066] The term "precursor" herein refers to those molecules or compounds that are reacted with each other and that are thus connected via crosslinks to form a polymer network and thus a hydrogel matrix. White other materials might be present in the hydrogel, such as travoprost or buffers, they are not referred to as "precursors".
[00067] The parts of the precursor molecules that are still present in a final polymer network are also ailed "units" herein. The "units" are thus the building blocks or constituents of a polymer network forming the hydrogel. For example, a polymer network suitable for use in the present disclosure may contain identical or different polyethylene glycol units as further disclosed herein. 5 '
[00068] The term "sustained release" for the-purposes of the present disclosure is meant to characterize products which are formulated to make travoprost (or another prostaglandin analogue) available over an extended period of time, thereby allowing a reduction in dosing frequency compared to an immediate release dosage form, such as a solution of travoprost that is topically applied onto the eye (such as travoprost-comprising eye drops). Other terms that may be used herein interchangeably with "sustained release" are "extended release" or "controlled 10 release". Within the meaning of the disclosure, the term "sustained release" comprises essentially constant travoprost release in vitro over a certain period of time.
[00069] ..... The terms "particles" or "microparticles" (such as "travoprost particles" and "travoprost microparticles") are used interchangeably herein. In some aspects of the present disclosure, a travoprost particle is a mixture of travoprost and a biodegradable polymer. In some embodiments, the travoprost particle consists of the 15 mixture of travoprost and the biodegradable polymer. In some embodiments, the travoprost particle essentially consists of the mixture of travoprost and the biodegradable polymer. The travoprost particles, for example, may -besides travoprost and the biodegradable polymer- further contain residual amounts of components from the manufacturing process, such as components from the continuous and / or dispersed phase (see, for example, Table 5 of Example 1 showing residual amounts of dichloromethane, DCM), In some embodiments, the biodegradable 20 polymer is a polylactide, such as poly(DL)lactide or poly(L)lactide. The microparticles of the present disclosure are spherical or essentially spherical. A "type" of a travoprost particle refers to a travoprost particle having specific properties and thus being distinguishable from other travoprost particle types. For example, a specific travoprost particle type can be defined as a travoprost particle having a specific biodegradable polymer that is different from the biodegradable polymer of another travoprost particle type. The specific biodegradable polymer might be a polylactide 25 with a specific inherent viscosity different from the specific inherent viscosity of other travoprost particle types, See Figure 2 for a schematic outline of an exemplary particle of the present disclosure. (00070] The term "median diameter" is used interchangeably herein with "D50". The "median diameter" or "D50" defines a specific property of a particle size distribution of travoprost particles. The median diameter refers to the diameter below which 50% of travoprost particles fall. As will be understood by a person of ordinary skill in the 30 art, the term "median diameter" and "average diameter" do not have the same definitions and normally do not match. The "median diameter" and the "average diameter" match only when the particle size distribution is symmetrical about the center. In some embodiments, the median diameter of the travoprost particles of the present disclosure is about 8 pm to about 13 pm.
[00071] The "particle size distribution" defines the relative amount of particles present according to size. 35- For example, one or more of the DIO, D50, and D90 values can be reported for a particle size distribution. The DIO value refers to the diameter below which 10% of travoprost particles fall, the D50 value (as outlined above) refers to the diameter below which 50% of travoprost particles fall, and the D90 value refers to the diameter below which 90% of travoprost particles fall. For example, DIO = 83 pm, dDSO = 330 pm, and D90 = 1600 pm means that 10% of the particles are smaller than 83 pm, 50% of the particles are smaller than 330 pm, and 90% of the particles are S smaller than 1600 pm.
[00072] The term "laser diffraction" refers to a measurement method for a particle size distribution or one or more values (such as the DIO, D50, and DOO values) characterizing a particle size distribution. An alternative measurement method for a particle size distribution or one or more values characterizing such a particle size ..... distrubtion is sieve analysis or, briefly, "sieving". A suitable laser diffraction method for determining the particle size 10 distribution or one or more values (such as the DIO, D50, and D90 values) characterizing a particle size distribution is described in detail herein in Example 1 below. The particle size distribution or one or more values (such as the DIO, D50, and D90 values) characterizing a particle size distribution are measured by laser diffraction using a Malvern Mastersizer 3000E. The parameters for measurement are given in Table 2 of the present application (e.g. the refractive index is 1.4589). 15
[00073] The term "polylactide" (also known as "polylactic acid" or "PLA") as used herein refers to homopolymere obtained by polycondensation of lactic acid. In other words, a polylactide consists of lactic acid monomer units. Such polylactide can have an add or an ester end group but is not constituted of other monomer units in the polymer backbone such as is the case in polylactide-co-glycolide. Polylactide can be formed by polymerization of D-Lactic acid, L-Lactic acid, or any mixture of D-lactic acid and L-lactic acid (the latter might be 20 referred to as "poly(DL)lactide").
[00074] The term "inherent viscosity" is used tc denote a physical parameter of the polylactides (PLAs) used herein. The different molecular weight polymers are described as, for example, 4A, 7A, 9A and 5.5E PLA where the numerical value designates the target inherent viscosity (IV) of the polymer in chloroform which correlates to the PLA molecular weight and the letter suffix designates acid (A) or ester (E) end group. When measured in 0.5 % w / v 25 chloroform at 30 °C, 4A PLA has an inherent viscosity of 0.35 to 0.45 dl / g; 7A PLA has an inherent viscosity of 0.60 to 0.80 dl / g and 9A PLA has an inherent viscosity of 0.80 to 1.0 dl / g. When measured in 0.1 % w / v chloroform at 25 °C, 5.5E PLA has an inherent viscosity of 0.55 to 0.75 dl / g. [0007S] The term "travoprost burst" as used herein denotes a rapid initial release of travoprost from an intracameral implant within a relatively short interval after insertion, e.g. within the first day following insertion. In 30 some embodiments, the initial travoprost release measured after 1 day (travoprost burst) under in vitro physiological conditions is between 10% and 20 % or less than 20% based on the total amount of travoprost in the intracameral implant. Suitable in vitro physiological conditions are simulated physiological sink conditions in 50 mL of lx PBS, 0.5% PEG-40 hydrogenated castor oil, 0.01% sodium fluoride buffer at pH 7.2-7.4 at 37 °C.
[00076] The term “visualization agent" as used herein refers to a molecule or composition that is contained within the hydrogel of an implant providing the possibility to easily visualize the implant when inserted into the anterior chamber of a subject's eye. The visualization agent may be a fluorophore such as fluorescein, rhodamine, coumarin, and cyanine. In certain embodiments the visualization agent is fluorescein or includes a fluorescein moiety.
[00077] As used herein, "membrane emulsification" is a method for preparing microparades. During membrane emulsification, a dispersed phase (which is a hydrophobic phase) containing the active ingredient is passed through a membrane of a certain pore size into a continuous phase (which is a hydrophilic phase). Particles are produced as droplets of dispersed phase that are sheared off by the continuous phase as they pass through the pores of the membrane. In some embodiments, the dispersed phase constitutes polylactide and travoprost dispersed in dichloromethane. In some embodiments, the continuous phase constitute polyvinyl alcohol in water, such as RODI (reverse osmosis deionized) water. In some embodiments, the membrane pore size is from about 2.5 pm to about 7.5 pm. In some embodiments, the membrane pore size is from about 3 pm to about 7 pm. In some embodiments, the membrane pore size is from about 4 pm to about 6 pm. In some embodiments, the membrane pore size is about 5 pm. Examples of suitable membrane emulsification apparatuses are an AXF-Mini (Micropore Technologies, United Kingdom) and an LDC-1 (Micropore Technologies, United Kingdom). See also Example 1.
[00078] As used herein, the term "aqueous humor" refers to the liquid within the anterior chamber.
[00079] As used herein, the term "bilaterally" or "bilateral" refers -in the context of administration / insertion of the implants or travoprost particles of the present disclosure- to an administration / insertion of the implants or travoprost particles into both eyes of a subject in need of treatment. Treatment thus occurs independent for each of the subject's eyes.
[00080] The term "treat", "treating" or”treatment" refer to reversing, alleviating, delaying the onset of, or inhibiting the progress of a disclosed condition (e.g., ocular hypertension or glaucoma), or one or more symptoms thereof, as described herein. A symptom associated with ocular hypertension or glaucoma to be treated may be a high intraocular pressure (IOP) that needs to be reduced. In other aspects, a subject may be treated in the absence of symptoms. For example, a susceptible individual may be treated prior to the onset of symptoms (e.g., in light of a history of symptoms and / or in light of exposure to a particular organism, or other susceptibility factors), i.e., prophylactic treatment. Treatment may also be continued after symptoms have resolved, for example to delay their recurrence. In some embodiments, in the context of treatment, a therapeutically effective amount of travoprost (tn form of an intracameral implant of the present disclosure or travoprost particles of the present disclosure) is administered to the subject. As used herein, the term "therapeutically effective" refers to the amount of travoprost needed to produce a desired therapeutic result after administration. For example, in the context of the present disclosure, one desired therapeutic result would be the reduction of the IOP, e.g., as measured by in vivo teste known to the person of ordinary skill in the art. Amounts and doses of travoprost as provided herein refer to the isopropyl ester.
[00081] The term^'subj^ be used interchangeably and mean a mammal in need of treatment. Examples of mammals may be human, companion animals (e.g., dogs, cats, and the tike), farm animals (e.g., cows, pigs, horses, sheep, goats and the like) and laboratory animals (e.g., rats, mice, guinea pigs and the like). In some embodiments, the subject is a human in need of treatment. 5
[00082] As used herein, the term "intraocular p'essure" (I0P) is the fluid pressure inside the eye. Tonometry, such as Goldmann tonometry, is generally the method eye care professionals use to determine IOP.
[80083] As used herein, the term "glaucoma" may encompass the forrhs of open-angle glaucoma and angle-closure glaucoma. Subtypes of open-angle glaucoma disclosed herein may encompass normal-tension glaucoma, congenital glaucoma, secondary glaucoma, pigmentary glaucoma, pseudoexfoliative glaucoma, traumatic 10 glaucoma, neovascular glaucoma, irido corneal endothelial syndrome (ICE), and / or uveitic glaucoma. As used herein, the term "open-angle glaucoma" is classified by ICD-10 Code H40. Open-angle glaucoma may be roughly classified into mild, moderate or severe open angle glaucoma.
[00084] As used herein, "ocular hypertension" usually refers to any situation in which the pressure Inside the eye, i,e. IOP, is higher than normal. Eye pressure is measured in millimeters of mercury (mm Hg). Normal eye 15 pressure is 21 mm Hg and lower, with an average of 16 mm Hg. Ocular hypertension is usually an eye pressure of above 21 mm Hg , The eye pressure is connected to the corneal thickness of an individual subject. Individuals with a thin cornea may have ocular hypertension despite of an intraocular eye pressure of below 21 mm Hg and individuals with a thick cornea may have normal eye pressure despite of an intraocular eye pressure of above 21 mm Hg. Therefore, it is also usual to apply a correction factor for the variation of the corneal thickness. 20...... DETAILED DESCRIPTION
[00085] In the following, farther aspects and embodiments of the present disclosure are described. Travoprost
[00086] In some aspects, the intracameral implants and particles of the present disclosure comprise 25 travoprost ......
[00087] The IUPAC name of travoprost is (isopropyl (Z)-7- [(1R,2R,3R,55)-3,5-dihydroxy-2-[(lE,3R)-3-hydroxy-4-[(<i,u,<z-trifluoro-m-isopropyl-tolyl)oxy]-l-butenyl]-cyclopentyl]-5-heptenoate. Travoprost is a prodrug of travoprost acid. The molecular structures of travoprost and travoprost acid are shown in the below scheme: ,0 Travoprost R = isopropyl Travoprost acid R = H
[00088] The conversion of travoprost to travoprost acid is shown in the below scheme: Iravoprost
[00089] Travoprost free add (also referred to as fluprostenol) is a prostaglandin F2o analogue and a highly 5 selective agonist of the prostaglandin F receptor (FP receptor)binding said receptor with a high affinity. Compared to latanoprost, the free acid of travoprost was observed to have higher potency and greater selectivity for the FP receptor based on results from in vitro binding affinity studies.
[00090] Travoprost acid (as endogenous prostaglandin F2o and other prostaglandin F2a analogues) is believed to reduce intraocular pressure by increasing trabecular meshwork and uveoscleral outflow (Um, K.S., et al, 10 Mechanism of action of bimatoprost, latanoprost, and travoprost in healthy subjects. A crossover study. Ophthalmology, 2008. 115(5): p. 790-795 e4 and Toris, C.B., B.A.T. Gabelt, and P.L. Kaufman, Update on the Mechanism of Action of Topical Prostaglandins for Intraocular Pressure Reduction. Survey of Ophthalmology, 2008. 53(6, Supplement): p. S107-S120),
[00091] Although travoprost is a prodrug of travoprost acid (such as latanoprost being a prodrug of 15 latanoprost acid), for the purpose of the present disclosure, also travoprost (and other prodrugs such as latanoprost) are referred to herein as "prostaglandin analogues". The expression "prostaglandin analogues" is used herein as an abbreviation for "prostaglandin F2o analogues".
[00092] Travoprost as prodrug facilitates corneal penetration and affords delivery of the active carboxylic acid (travoprost add) to the aqueous humor. The prodrug ester is believed to be hydrolyzed by esterases in the 20 cornea to the biologically active free acid in which carbons 17-20 have been substituted with a meta trifluoromethylphenoxygroup. Sectorex^ DeSantis, and MA. Metiand, Travoprost: a potent ocular hypotensive agent. Drugs Today (Bare), 2003. 39(1): p. 61-74).
[00093] Travoprost is a clear, colorless to slightly yellow oil essentially insoluble in water. Travoprost is soluble in organic solvents such as methanol, ethanol, chloroform, dichloromethane, and acetonitrile. 5 Travoprost particles
[00094] In some aspects, the present disclosure is directed to travoprost particles, wherein the travoprost particles are a mixture of travoprost and a biodegradable polymer. In some embodiments, the travoprost particles have a median diameter of about 2 pm to about 19 pm as determined by laser diffraction.
[00095] In some embodiments, the travoprost particles have a median diameter of about 3 pm to about 19 10 pm as determined by laser diffraction. In some embodiments, the travoprost partides have a median diameter of about 4 pm to about 17 pm as determined by laser diffraction. In some embodiments, the travoprost particles have a median diameter of about 5 pm to about 16 pm as determined by laser diffraction. In some embodiments, the travoprost particles have a median diameter of about 6 pm to about 15 pm as determined by laser diffraction. In some embodiments, the travoprost particles have a median diameter of about 7 pm to about 14 pm as determined 15 by laser diffraction.
[00096] In some embodiments, the travoprost particles have a median diameter of about 8 pm to about 13 pm as determined by laser diffraction.
[00097] In some embodiments, the travoprost particles have a median diameter of about 7 pm to about 10 pm as determined by laser diffraction. In some embodiments, the travoprost particles have a median diameter of 20 about 8 pm to about 9 pm as determined by laser diffraction. In some embodiments, the travoprost particles have a median diameter of about 8 pm or about 9 pm as determined by laser diffraction.
[00098] In some embodiments, the travoprost particles have a median diameter of about 9 pm to about 14 pm as determined by laser diffraction. In some embodiments, the travoprost particles have a median diameterof about 10 pm to about 13 pm as determined by laser diffraction. In some embodiments, the travoprost particles have 25 a median diameter of about 10 pm to about 12 pm as determined by laser diffraction. In some embodiments, the travoprost particles have a median diameter of about 12 pm to about 14 pm as determined by laser diffraction. In some embodiments, the travoprost particles have a median diameter of about 9 pm to about 11 pm as determined by laser diffraction. In some embodiments, the travoprost partides have a median diameter of about 10 pm or about 11 pm as determined by laser diffraction. In some embodiments, the travoprost particles have a median diameter of 30 about 12 pm or about 13 pm as determined by laser diffraction.
[00099] In some embodiments, the particle size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 2 pm to about 10 pm, D50 of about 6 pm to about 15 pm, and D90 of up to about 50 pm, such as 090 of about 12 to about 26 pm. In some embodiments, the particle size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 3 pm to about 9 pm, D50 of about 7 pm to about 14 pm, and D90 of up to about 50 pm, such as D90 of about 12 to about 26 pm. 5 [000100] In some embodiments, the particle size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 5 pm to about 9 pm, D50 of about 9 pm to about 14 pm, and D90 of about 13 pm to about 26 pm. In some embodiments, the particle size distribution of the travoprost particles as determined by laser diffraction is characterized as follows; DIO of about 6 pm to about 8 pm, D50 of about 10 pm to about 13 pm, and D90 of about 14 pm to about 25 pm. In some embodiments, the particle size 10 distribution of the travoprost particles as determined by laser diffraction is characterized as follows: D10 of about 8 pm, D50 of about 12 pm, and D90 of about 15 pm. In some embodiments, the partide size dlstributton of the travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 6 pm, D50 of about 10 pm, and D90 of about 14 pm. In some embodiments, the particle size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 6 pm, D50 of about 13 pm, and D90 of 15 about 25 pm. [000101] In some embodiments, the particle size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 3 pm to about 6 pm, D50 of about 7 pm to about 10 pm, and D90 of about 12 pm to about 16 pm. In some embodiments, the particle size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 4 pm to about 5 pm, D50 of 20 about 8 pm to about 9 pm, and D90 of about 13 pm to about 15 pm. In some embodiments, the particle size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 5 pm, D50 of about 9 pm, and D90 of about 14 pm. In some embodiments, the particle size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 5 pm, D50 of about 8 pm, and D90 of about 13 pm. In some embodiments, the particle size distribution of the travoprost particles as ..... 25 determined by laser diffraction is characterized as follows: DIO of about 4 pm, D50 of about 8 pm, and D90 of about 13 pm. In some embodiments, the particle size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 5 pm, DSO of about 9 pm, and D90 of about 15 pm. [000102] In some embodiments, the travoprost particles comprise about 40 wt-% to about 50 wt-% or about 41 wt-% to about 49 wt-% travoprost based on the total mass of the travoprost particles. In some 30 embodiments, the travoprost particles comprise about 42 wt-% to about 48 wt-% or about 43 wt-% to about 47 wt-% travoprost based on the total mass of the travoprost particles. [000103] In some embodiments, the travoprost particles comprise about 42 wt-% to about 44 wt-% travoprost based on the total mass of the travoprost particles. In some embodiments, the travoprost particles comprise about 45 wt-% to about 47 wt-% travoprost based on the total mass of the travoprost particles. In some embodiments, the travoprost particles comprise about 46 wt-% to about 48 wt-% travoprost based on the total mass of the travoprost particles. [000104] In some embodiments, the travoprost particles comprise about 43 wt-% travoprost based on the total mass of the travoprost particles. In some embodiments, the travoprost particles comprise about 46 wt-% travoprost based on the total mass of the travoprost particles. In some embodiments, the travoprost particles comprise about 47 wt-% travoprost based on the total mass of the travoprost partides. [000105] In some embodiments, the travoprost particles comprise about 40 wt-% to about 47 wt-% or about 41 wt-% to about 46 wt-% travoprost based on the total mass of the travoprost particles. In some embodiments, the travoprost particles comprise about 45 wt-% to about 47 wt-% or about 41 wt-% to about 43 wt-% or about 40 wt-% to about 42 wt-% travoprost based on the total mass of the travoprost particles, [000106] In some embodiments, the travoprost particles comprise about 46 wt-% travoprost based on the total mass of the travoprost particles. In some embodiments, the travoprost particles comprise about 42 wt-% travoprost bassi on the total mass of the travoprost particles. In some embodiments, the travoprost particles comprise about 41 wt-% travoprost based on the total mass of the travoprost particles. [000107] In some embodiments, the biodegradable polymer comprises or consists of: a polylactide-co-glycolide, a polylactide, a polyglycolide, a polycaprolactone, a polydioxanone, a polylactide-co-caprolactone or a mixture of any of the aforementioned. [000108] In some embodiments, the biodegradable polymer comprises or consists of a polyglycolide, such as poly(glycolide-co-L-lactide). [000109] In some embodiments, the biodegradable polymer comprises or consists of a polycaprolactone or a polylactide-co-caprolactone. In some embodiments, the biodegradable polymer comprises or consists of a poly(DL)lactide-co-caprolactone or a poly(L)lactide-co-caprolactone. [000110] In some embodiments, the biodegradable :polymer comprises or consists of a polylactide-co-glycolide. In some embodiments, the biodegradable polymer comprises or consists of a polylactide. In some embodiments, the biodegradable polymer comprises or consists of a mixture of a polylactide and a polylactide-co-glycolide. In some embodiments, the biodegradable polymer comprises or consists of a poly(L)lactide-co-glycolide or a poly(DL)lactide-co-glycolide. In some embodiments, the biodegradable polymer comprises or consists of a poly(L)lactide. In some embodiments, the biodegradable polymer comprises or consists of a poly(DL)lactide. In some embodiments, the biodegradable polymer comprises or consists of a poly(L)lactide-co-(DL)lactide. [G00111J In some embodiments, the biodegradable polymer comprises or consists of a poly(DL)lactide. [000112] In some embodiments, the biodegradable polymer comprises or consists of a poly(IX)la<*de. In some embodiments, the biodegradable polymer comprises or consists of a polylactide and wherein the polylactide has an acid end group, optionally wherein the polylactide is a poly(DL)lactide. In some embodiments, the biodegradable polymer comprises or consists of a polylactide and wherein the polylactide has an ester end group, 5 optionally wherein the polylactide is a poly(DL)lactide. [000113] In some embodiments, the travoprost particles are a mixture of travoprost and a biodegradable polymer consisting of a polylactide, wherein said polylactide: -has an inherent viscosity specification from about 0.50 dl / g to about 1.10 dl / g, such as about 0.60 dl / g to about 1,00 dl / g, as measured at 0.5% w / v in chloroform at 30°C, and optionally has an acid end group, 10-- or -has an an inherent viscosity specification from about 0.45 dl / g to about 0.85 dl / g, such as about 0.55 dl / g to about 0.75 dl / g, as measured at 0.1% w / v In chloroform at 25°C, and optionally has an ester end group. [000114] In some embodiments, the travoprost particles are a mixture of travoprost and a biodegradable polymer consisting of a polylactide having an acid end group and an inherent viscosity specification from about 0.25 15 dl / g to about 0.55 dl / g, such as about 0.35 dl / g to about 0,45 dl / g, as measured at 0.5% w / v in chloroform at 30°C. In some of these embodiments, the travoprost particles comprise about 44 wt-% to about 48 wt-%, such as about 45 wt-% to about 47 wt-% or about 46 wt-%, travoprost based on the total mass of the travoprost particles. In some of these embodiments, the particle size distribution of said travoprost particles as determined by laser diffraction Is characterized as follows: DIO of about 4 pm to about 6 pm, D50 of about 8 pm to about 10 pm, and 20 D90 of about 13 pm to about 15 pm. In some of these embodiments, the particle size distribution of said travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 5 pm, D50 of about 9 pm, and 090 of about 14 pm. In some of these embodiments, the particle size distribution of said travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 7 pm to about 9 pm, D50 of about 11 pm to about 13 pm, and D90 of about 14 pm to about 16 pm. In some of these embodiments, the particle size distribution-25 of said travoprost particles as determined by laser diffraction is characterized as follows: D10 of about 8 pm, D50 of about 12 pm, and D90 of about 15 pm. [000115] In some embodiments, the travoprost particles are a mixture of travoprost and a biodegradable polymer consisting of a polylactide having an acid end group and an inherent viscosity specification from about 0.50 dl / g to about 0.90 dl / g, such as about 0.60 dl / g to about 0.80 dl / g, as measured at 0.5% w / v in chloroform at 30’C. 30 In some of these embodiments, the travoprost particles comprise about 45 wt-% to about 49 wt-%, such as about 46 wt-% to about 48 wt-% or about 47 wt-%, travoprost based on the total mass of the travoprost particles. In some of these embodiments, the particle size distribution of said travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 4 pm to about 6 pm, D50 of about 7 pm to about 9 pm, and D90 of about 12 pm to about 14 pm. In some of these embodiments, the particle size distribution of said travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 5 pm, D50 of about 8 pm, and DW of about 13 pm. [000116] In some embodiments, the travoprost particles are a mixture of travoprost and a biodegradable polymer consisting of a polylactide having an acid end group and an inherent viscosity specification from about 0.70 dl / g to about 1.10 dl / g, such as about 0.80 dl / g to about 1.00 di / g, as measured at 0.5% w / v in chloroform at 30°C. In some of these embodiments, the travoprost particles comprise about 41 wt-% to about 45 wt-%, such as about 42 wt-% to about 44 wt-% or about 43 wt-%, travoprost based on the total mass of the travoprost particles. In some of these embodiments, the travoprost particles comprise about 40 wt-% to about 44 wt-%, such as about 41 wt-% to about 43 wt-% or about 42 wt-%, travoprost based on the total mass of the travoprost particles. In some of these embodiments, the particle size distribution of said travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 3 pm to about 5 pm, D50 of about 7 pm to about 9 pm, and D90 of about 12 pm to about 14 pm. In some of these embodiments, the particle size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 4 pm, D50 of about 8 pm, and D90 of about 13 pm. In some of these embodiments, the particle size distribution of said travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 5 pm to about 7 pm, D50 of about 9 pm to about 11 pm, and D90 of about 13 pm to about 15 pm. In some of these embodiments, the particle size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 6 pm, D50 of about 10 pm, and D90 of about 14 pm. [000117] In some embodiments, the travoprost particles are a mixture of travoprost and a biodegradable polymer consisting of a polylactide having an ester end group and an inherent viscosity specification from about 0.45 dl / g to about 0.85 dl / g, such as about 0.55 dl / g to about 0.75 dl / g, as measured at 0.1% w / v in chloroform at 25°C. In some of these embodiments, the travoprost particles comprise about 41 wt-% to about 45 wt-%, such as about 42 wt-% to about 44 wt-% or about 43 wt-%, travoprost based on the total mass of the travoprost partides, In some of these embodiments, the travoprost particles comprise about 39 wt-% to about 43 wt-%, such as about 40 wt-% to about 42 wt-% or about 41 wt-%, travoprost based on the total mass of the travoprost particles. In some of these embodiments, the particle size distribution of said travoprost particles as determined by laser diffraction is characterized as follows: D10 of about 4 pm to about 6 pm, D50 of about 8 pm to about 10 pm, and D90 of about 14 pm to about 16 pm. In some of these embodiments, the partide- size distribution of the travoprost paitldes as determined by laser diffraction is characterized as follows: DIO of about 5 pm, D50 of about 9 pm, and D90 of about 15 pm. In some of these embodiments, the particle size distribution of said travoprost particles as determined by laser diffraction is characterized as follows: D10 of about 5 pm to about 7 pm, D50 of about 12 pm to about 14 pm, and D90 of about 24 pm to about 26 pm. In some of these embodiments, the particle size distribution of the travoprost particles as determined by taser diffraction is characterized as follows: D10 of about 6 pm, D50 of about 13 pm, and D90 of about 25 pm. [000118] In some embodiments, the travoprost particles essentially consist of the mixture of travoprost and the biodegradable polymer. The term “essentially consist used herein allows for die presence of further components that not materially affect the essential characteristics of the travoprost particles as described herein. An example of further components that not materially affect the essential characteristics of the travoprost particles as 5 described herein are pharmaceutically acceptable residual amounts of manufacturing components, such as dichloromethane (see, for example, Table 5 of Example 1 showing residual amounts of dichloromethane, DCM). [000119] In some embodiments, the travoprost particles consist of the mixture of travoprost and the biodegradable polymer. [000120] In some embodiments, the travoprost particles are obtained by or are obtainable by a process 10 comprising a membrane emulsification step. The membrane emulsification may be carried out using an AXF-Mini apparatus (Micropore Technologies, United Kingdom) or an LDC-1 appartus (Micropore Technologies, United Kingdom). [000121] In some embodiments, the travoprost particles are obtained by or are obtainable by a process comprising^ 15 -providing or preparing a first solution comprising travoprost and the biodegradable polymer, -providing or preparing a second solution, wherein the second solution is an aqueous solution, and -passing the first solution through a membrane with pores into the second solution to provide the travoprost particles, optionally wherein the membrane pore size is from about 2.5 pm to about 7,5 pm, such as about 5 pm. 20 [000122] In some embodiments, the travoprost particles are obtained by or are obtainable by a process comprising: -providing or preparing a first solution wmprising travoproa and the biodegradable polymer, -providing or preparing a second solution, wherein the second solution Is an aqueous solution, -passing the first solution through a membrane with pores into the second solution to provide the travoprost 25 particles, optionally wherein the membrane pore size is from about 2.5 pm to about 7.5 pm, such as about 5 pm, and -hardening the travoprost particles. [000123] In some embodiments, the travoprost particles are obtained by or are obtainable by a process comprising: -providing or preparing a first solution comprising travoprost and the biodegradable polymer, -providing or preparing a second solution, wherein the second -solution Is an aqueous solution, -passing the first solution through a membrane with pores into the second solution to provide the travoprost particles, optionally wherein the membrane pore size is from about 2.5 pm to about 7.5 pm, such as about 5 5 pm, -hardening the travoprost particles, and -purifying the hardened travoprost particles. [000124] In some embodiments, the travoprost particles are obtained by or are obtainable by a process comprising: 10 -providing or preparing a first solution comprising travoprost and the biodegradable polymer, -providing or preparing a second solution, wherein the second solution is an aqueous solution, -passing the first solution through a membrane with pores into the second solution to provide the travoprost particles, optionally wherein the membrane pore size is from about 2.5 pm to about 7.5 pm, such as about 5 m ..... ...... ..... 15 -hardening the travoprost particles, -purifying the travoprost particles, and -drying the travoprost particles. [000125] Typically, when the first solution is passed through the membrane with pores into the second solution, the travoprost particles are produced as droplets of the first solution that are sheared off by the second solution as 20 they pass through the pores of the membrane. ...... [000126] In some embodiments, the first solution is an organic solution of travoprost and the biodegradable polymer. In some embodiments, the first solution is an organic solution of travoprost and the biodegradable polymer, wherein the organic solvent is dichloromethane. In some embodiments, the concentration of the biodegradable polymer in the first solution is from about 30 % w / v to about 40% w / v, such as about 35% w / v, and the concentration of 25 travoprost in the first solution is from about 20% to about 35% w / v, such as about 25% to about 30% w / v. In some embodiments, the concentration of the biodegradable polymer in the first solution is from about 20 % w / v to about 45% w / v and the concentration of travoprost in the first solution is from about 40 % to about 65% w / v, such as about 50% w / v. The first solution is commonly also referred to as the dispersed phase or DP in a membrane emulsification process. The dispersed phase Is a single-phase solution, i [000127] In some embodiments, the second solution is an aqueous solution of an alcohol. In some embodiments, the second solution is an aqueous solution of polyvinyl alcohol. In some embodiments, the second solution is an aqueous solution of polyvinyl alcohol at about 0.5% w / w to about 1.5% w / w, such as about 1% w / w, polyvinyl alcohol. In some embodiments, the water used for preparing the second solution Is RODI water. Polyvinyl alcohol is considered to act as emulsifier. The second solution is commonly also referred to as the continuous phase or CP in a membrane emulsification process. [000128] In some embodiments, the flow rate of the first solution when passing through the membrane is maintained at about 0.10 mL / min to about 0.40 mL / min, such as at about 0.125 mL / min. In some embodiments, the flow rate of the first solution when passing through the membrane is maintained at about 0.20 mL / min to about 0.30 mL / min, such as at about 0.25 mL / mln. [000129] In some embodiments, the flow rate of the second solution into which the first solution is passed through the membrane pores is maintained at about 60 to about 90 mL / min, such as at about 70 to about 80 mL / min. [000130] In some embodiments, the first solution is an organic solution of travoprost and the biodegradable polymer and the organic solvent Is evaporated and extracted during hardening toe travoprost particles, in some embodiments, the organic solvent is dichloromethane. [000131] In some embodiments, hardening the travoprost particles is carried out for at least about 12 hours or for at least about 16 hours or from about 18 hours to about 24 hours. In some embodiments, hardening the travoprost particles is carried out under stirring and / or under a nitrogen sweep. [000132] In some embodiments, the hardened travoprost particles are purified by centrifugation, tangential flow filtration, or a combination thereof. In some embodiments, the hardened travoprost particles are purified by tangential flow filtration. In some embodiments, the harcened travoprost particles when purifying are concomitantly . also concentrated. [000133] In some embodiments, drying the travoprost particles comprises or consists of lyophilizing the travoprost particles. [000134] In other aspects, the present disclosure is also directed to travoprost particles that are not a mixture of travoprost and the biodegradable polymer (see, for example, the schematic overview in Figure 2 showing travoprost mixed into PLA), but that consist or essentially consist of travoprost microencapsulated in the biodegradable polymer. In some embodiments, travoprost is microencapsulated with poly(lactic-co-glycolic acid) (PlGA) or po!y(latfic acid) (PLA), Or a combination thereof. In some embodiments, travoprost is microencapsulated with PLA. (000135] In another aspect, the present disclosure is also directed to the microparticles as described above containing another active pharmaceutical ingredient instead of travoprost or a mixture of another pharmaceutical 5 ingredient with travoprost. In some embodiments, the other active pharmaceutical ingredient is another prostaglandin analogue. Examples of other prostaglandin analogues are latanoprost, tafluprost, bimatoprost, unoprostone, unoprostone isopropyl ester, and latanoprostene bunod. Thus, in some embodiments, the present disclosure Is directed to particles being a mixture of a ■prostaglandin-analogue and a biddegradable polymer, wherein the particles have a median diameter of about 2 pm to about 19 pm, such as about 8 pm to about 13 pm, as 10 determined by laser diffraction. In some embodiments, the biodegradable polymer comprises or consists of a polyiactide, optionally with an add or ester end group. In some embodiments, the prostaglandin analogue is bimatoprost. In some embodiments, the prostaglandin analogue is latanoprost. In some embodiments, the prostaglandin analogue is tafluprost. Unoprostene <Lat#neprostene bunpd Method of Manufacturing Travoprost Particles [000136] In a further aspect, the present disclosure is directed to a method of manufacturing travoprost particles, wherein the travoprost particles are a mixture of travoprost and a biodegradable polymer and wherein the method comprises a membrane emulsification step. The membrane emulsification may be carried out using an AXF-5 Mini apparatus (Micropore Technologies, United Kingdom) or an LDC-1 appartus (Micropore Technologies, United Kingdom)., [000137] In a further aspect, the present disclosure is directed to a method of manufacturing travoprost particles, wherein the travoprost particles are a mixture of travoprost and a biodegradable polymer and wherein the method comprises: 10 -providing or preparing a first solution comprising travoprost and the biodegradable polymer, -providing or preparing a second solution, wherein the second solution is an aqueous solution, and -passing the first solution through a membrane with pores into the second solution to provide the travoprost particles [000138] In a further aspect, the present disclosure is directed to a method of manufacturing travoprost: 15 particles, wherein the travoprost particles are a mixture of travoprost and a biodegradable polymer and wherein the method comprises: -providing or preparing a first solution comprising fravopro^ and the biodegradable polymer, -providing or preparing a second solution, wherein the second solution is an aqueous solution, -pasting the first solution thraugh a membrane wtt pores into the second solution to provide the travoprost 20 particles, and -hardening the travoprost particles, [000139] In a further aspect, the present disclosure is directed to a method of manufacturing travoprost particles, wherein the travoprost particles are a mixture of travoprost and a biodegradable polymer and wherein the method comprises: :• 25 -providing or preparing a first solution comprising travoprost and the biodegradable polymer, -providing or preparing a second solution, wherein the second solution is an aqueous solution, -passing the first solution through a membrane with pores into the second solution to provide the travoprost partides, -hardening the travoprost particles, and -purifying the hardened travoprost particles. 5 [000X40] In a further aspect, the present disclosure is directed to a method of manufacturing travoprost particles, wherein the travoprost particles are a mixture of travoprost and a biodegradable polymer and wherein the method comprises: -providing or preparing a first solution comprising travoprost and the biodegradable polymer, -providing or preparing a second solution, wherein the second solution is an aqueous solution, 10 -passing the first solution through a membrane with pores into the second solution to provide the travoprost particles,- -hardening the travoprost particles, -purifying the travoprost particles, and -drying the travoprost particles. 15 [000141] Typically, when the first solution is passed through the membrane with pores into the second solution, the travoprost particles are produced as droplets of the first solution that are sheared off by the second solution as they pass through the pores of the membrane. [000142] In some embodiments, the membrane pore size is from about 2.5 pm to about 7.5 pm. In some embodiments, the membrane pore size is from about 3 pm to about 7 pm. In some embodiments, the membrane 20 pore size is from about 4 pm to about & pm, [000143] In some embodiments, the membrane pore size is about 5 pm. [000144] In some embodiments, the first solution is an organic solution of travoprost and the biodegradable polymer. In some embodiments, the organic solvent is dlchtoromethane. In some embodiments, the concentration of the biodegradable polymer in the first solution is from about 30 % w / v to about 40% w / v, such as about 35% w / v, 25 and the concentration of travoprost in the first solution is from about 20% to about 35% w / v, such as about 25% to about 30% w / v. In some embodiments, the concentration of the biodegradable polymer in the first solution is from about 20% w / v to about 45% w / v and the concentration of travoprost in the first solution is from about 40% to about 65% w / v, such as about 50% w / v. The first solution is commonly also referred to as the dispersed phase or DP In a membrane emulsification process. [000145] In some embodiments, the second solution is an aqueous solution of an alcohol. In some embodiments, the second solution is an aqueous solution of polyvinyl alcohol. In some embodiments, the second 5 solution is an aqueous solution of polyvinyl alcohol at about 0.5% w / w to about 1.5% w / w, such as about 1% w / w, polyvinyl alcohol. In some embodiments, the water used for preparing the second solution is RODI water. Polyvinyl alcohol is considered to act as emulsifier. The second solution is commonly also referred to as the continuous phase or CP in a membrane emulsification process. [000146] In some embodiments, the flow rate of the -first solution when passing through the membrane is 10 maintained at about 0.10 mL / min to about 0.40 mL / min, such as at about 0.125 mL / min, In some embodiments, the flow rate of the first solution when passing through the membrane is maintained at about 0.20 mL / min to about 0.30 mL / min, such as at about 0.25 mL / min. [000147] In some embodiments, the first solution is an organic solution of travoprost and the biodegradable polymer and wherein the organic solvent is evaporated and extracted during hardening the travoprost particles, 15 optionally wherein the organic solvent is dichloromethane. [000148] In some embodiments, hardening the travoprost particles is conducted for at least about 12 hours or for at least about 16 hours or from about 18 hours to about 24 hours. In some embodiments, hardening the travoprost particles is carried out under stirring and / or under a nitrogen sweep. [000149] In some embodiments, the hardened travoprost particles are purified by centrifugation, tangential 20 flow filtration, or a combination thereof. In some embodiments, the hardened travoprost particles are purified by tangential flow filtration. In some embodiments, purifying the hardened travoprost particles concomitantly ■concentrates the hardened travoprost particles. [000150] In some embodiments, drying the travoprost particles comprises or consists of lyophilizing the travoprost particles...... 25 [000151] In some embodiments, the biodegradable polymer is defined as described above in the Chapter "Travoprost particles". For example, in some embodiments the biodegradable polymer comprises or consists of a polylactide, such as a poly(DL)lactide. As described above, the polylactide may have an acid end group or an ester end group. In some embodiments, the polylactide has an inherent viscosity specification from about 0.50 dt / g to about 1.10 dl / g, such as about 0.60 dl / g to about 1.00 dt / g, as measured at 0.5% w / v in chloroform at 30°C, and 30 optionally has an acid end group. In some embodiments, the polylactide has an an inherent viscosity specification from about 0,45 dl / g to about 0.85 dl / g, such as about 0.55 dl / g to about 0.75 dl / g, as measured at 0.1% w / v in chloroform at 25OC, and optionally has an ester end group. [000152] In some embodiments, the travoprost particles manufactured by the method as described in this Chapter ("Method of Manufacturing Travoprost Particles") are described above in the Chapter "Travoprost particles". [000153] In some embodiments, the median diameter of the travoprost particles produced by the method of manufacturing travoprost particles is about 1 to about 60 pm. 5 [000154] In some embodiments, the median diameter of the travoprost particles produced by the method of manufacturing travoprost particles is about 20 to about 55 pm. In some embodiments, the biodegradable polymer of such travoprost partides consists of a polylacOde having an inherent viscosity of about 0.30 to about 1.00 dt / g as determined at 0.5% w / v in CHCb at 30 °C. [000155] In some embodiments, the median diameter of the travoprost particles produced by the method of 10 manufacturing travoprost particles is about 2 pm to about 19 pm, such as about 7 pm to about 14 pm. In some embodiments, the median diameter of the travoprost particles is about 8 pm to about 13 pm. In some embodiments, the median diameter of the travoprost particles is about 8 pm to about 9 pm. In some embodiments, the median diameter of the travoprost particles is about 10 pm to about 13 pm, such as about 10 pm, about 12 pm, or about 13 pm. 15 [000156] In a further aspect, the present disclosure is also directed to a method of manufacturing particles as described in this chapter ("Method of Manufacturing Travoprost Particles") wherein the particles comprise another active pharmaceutical ingredient instead of travoprost. In some embodiments, the other active pharmaceutical ingredient is another prostaglandin analogue. Examples of other prostaglandin analogues are latanoprost, tafluprost, bimatoprost, unoprostone, unoprostone isopropyl ester, and latanoprostene bunod. 20 [000157] In a further aspect, the present disclosure is also directed to travoprost particles obtainable by or obtained by the method of manufacturing travoprost particles as described in the present Chapter ("Method of Manufacturing Travoprost Parades"). Travoprost sustained release intracameral implant [000158] The present disclosure, in a further aspect, is directed to travoprost sustained release 25 biodegradable intracameral implant comprising a biodegradable hydrogel and travoprost particles, wherein the biodegradable hydrogel comprises a polymer network comprising one or more units of polyalkylene glycol, wherein the travoprost particles are a mixture of travoprost and a biodegradable polymer, wherein the travoprost particles are dispersed within the biodegradable hydrogel, and wherein the travoprost particles have a median diameter of about 2 pm to about 19 pm as determined by laser diffraction. [000159] In some embodiments, the intracameral implant is in form of a fiber. [000160] In some embodiments, the intracameral implant is designed for implantation into the anterior 5 chamber of a human eye. In some embodiments, the intracameral implant is designed for implantation into the iridocorneal angle of the anterior chamber of a human eye. In some embodiments, the intracameral implant has dimensions to fit Into the iridocorneal angle of a human eye. In some embodiments, the the intracameral implant has dimensions to fit into the iridocorneal angle of a human eye and to get fixated in said iridocorneal angle during the period of treatment of the human eye and / or until it is biodegraded. In some embodiments, the intracameral implant 10 after insertion into the iridocorneal angle of a human eye swells due to the uptake of aqueous humor and becomes increasingly soft before it dissolves and fully degrades. In some embodiments, the implant when in a dried state prior to insertion into a subject’s eye becomes hydrated once inserted into the eye. [000161] Under the following sub-chapters, further embodiments of the intracameral implant of the present disclosure are described. The headings are not intended to limit the described subject-matter in any way, in IS particular, embodiments under one heading (such as embodiments described under the heading "Travoprost particles") can be combined with embodiments under other headings (such as embodiments described under the heading "Biodegradable hydrogel"). ' IraygBrast_particles.....IP the intracameral implant [000162] For the travoprost particles in the intracameral implant of the present disclosure, reference is made 20 to the section "Travoprost particles" above. For example, in some embodiments, the biodegradable polymer consists of a polylactide, such as poly(DL)lactide. In some embodiments, the travoprost particles have a median diameter of about 7 pm to about 14 pm. In some embodiments, the travoprost particles have a median diameter of about 8 pm to about 13 pm. In some embodiments, the biodegradable polymer consists of a polylactide having an inherent viscosity specification from about 0.50 dl / g to about l.lQdl / g, such as about 0,60 dl / g to about 1.00 dl / g, as 25 measured at 0.5% w / v in chloroform at 30°C, and optionally having an acid end group. In some embodiments, the biodegradable polymer consists of a polylactide having an inherent viscosity specification from about 0.45 dl / g to about 0.85 dl / g, such as about 0.55 dl / g to about 0.75 dl / g, as measured at 0.1% w / v in chloroform at 25°C, and optionally having an ester end group. ...... [000163]- In some embodiments, the intracameral implant comprises only one type of travoprost particles. A 30 "type of a travoprost particles" refers to a travoprost particle having specific properties and thus being distinguishable from other travoprost particle types. For example, a specific "type of travoprost particles" as referred to herein, can be identified by travoprost particles with a specific biodegradable polymer. Different types of travoprost particles might thus be distinguished from each Otiier by including polylactides as biodegradable polymers having different inherent viscosities and / or different end groups. [000164] In some embodiments, the intracameral implant comprises only one type of travoprost particles, wherein said travoprost particles are a mixture of travoprost and a biodegradable polymer consisting of a polylactide, 5 wherein said polylactide: -has an inherent viscosity specification from about 0.50 dl / g to about 1.10 dl / g, such as about 0.60 dl / g to about 1.00 dl / g, as measured at 0.5% w / v In chloroform at 30°C, ahd optionally has an acid end group, or -has an inherent viscosity specification from about 0.45 dl / g to about 0.85 dl / g, such as about 0.55 dl / g to 10 about 0.75 dl / g, as measured at 0.1% w / v in chloroform at 25°C, and optionally has an ester end group. [000165] m some embodiments, the intracameral implant comprises only one type of travoprost particles, wherein said travoprost particles are a mixture of travoprost and a biodegradable polymer consisting of a polylactide having an add end group and an inherent viscosity specification from about 0.25 dl / g to about 0.55 dl / g, such as about 0.35 dl / g to about 0.45 dl / g, as measured at 0.5% w / v in chloroform at 30°C. In some of these embodiments, 15 said travoprost particles comprise about 44 wt-% to about 48 wt-%, such as about 45 wt-% to about 47 wt-% or about 46 wt-%, travoprost based on the total mass of the travoprost particles. In some of these embodiments, the particle size distribution of said travoprost particles as determined by laser diffraction is characterized as follows: D10 of about 4 pm to about 6 pm, D50 of about 8 pm to about 10 pm, and D90 of about 13 pm to about 15 pm. In some of these embodiments, the particle size distribution of said travoprost particles as determined by laser diffraction is 20 characterized as follows: D10 of about 5 pm, D50 of about 9 pm, and D90 of about 14 pm. In some of these embodiments, the particle size distribution of said travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 7 pm to about 9 pm, D50 of about 11 pm to about 13 pm, and D90 of about 14 pm to about 16 pm. In some of these embodiments, the particle size distribution of said travoprost particles as determined: by laser diffraction is characterized as follows; D10 of about 8 pm, D50 of about 12 pm, and D90 of 25 about IS pm. [000166] In some embodiments, the intracameral implant comprises only one type of travoprost particles, wherein said travoprost particles are a mixture of travoprost and a biodegradable polymer consisting of a polylactide having an acid end group and an inherent viscosity specification from about 0,50 dl / g to about 0.90 dl / g, such as about 0.60 dl / g to about 0.80 dl / g, as measured at 0.5% w / v in chloroform at 30°C. In some of these embodiments, 30 said travoprost particles comprise about 45 wt-% to about 49 wt-%, such as about 46 wt-% to about 48 wt-% or about 47 wt-%, travoprost based on the total mass of the travoprost particles. In some of these embodiments, the particle size distribution of said travoprost particles as determined by laser diffraction is characterized as follows: D10 of about 4 pm to about 6 pm, D50 of about 7 pm to about 9 pm, and D90 of about 12 pm to about 14 pm. In some of these embodiments, the particle size distribution of said travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 5 pm, D50 of about 8 pm, and D90 of about 13 pm. [000167] In some embodiments, the intracameral implant comprises only one type of travoprost particles, wherein said travoprost particles are a mixture of travoprost and a biodegradable polymer consisting of a polylactide 5- having an acid end group and an inherent viscosity specification from about 0.70 dl / g to about 1.10 dl / g, such as about 0.80 dl / g to about 1.00 dl / g, as measured at 0.5% w / v in chloroform at 30°C. In some of these embodiments, said travoprost particles comprise about 41 wt-% to about 45 wt-%, such as about 42 wt-% to about 44 wt-% or about 43 wt-%, travoprost based on the total mass of the travoprost particles. In some of these embodiments, said travoprost particles comprise about 40 wt-% to about 44 wt-%, such as about 41 wt-% to about 43 wt-% or about 42 wt-%, 10 travoprost based on the total mass of the travoprost particles. In some of these embodiments, the particle size distribution of said travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 3 pm to about 5 pm, D50 of about 7 pm to about 9 pm, and D90 of about 12 pm to about 14 pm. In some of these embodiments, the particle size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: D10 of about 4 pm, D50 of about 8 pm, and D90 of about 13 pm. In some of these embodiments, the 15 particle size distribution of said travoprost particles as determined by laser diffraction is characterized as follows: D10 of about 5 pm to about 7 pm, DSO of about 9 pm to about 11 pm, and D90 of about 13 pm to about 15 pm. In some of these embodiments, the particle size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 6 pm, D50 of about 10 pm, and D90 of about 14 pm. [000168] In some embodiments, the intracameral implant comprises only one type of travoprost particles, 20 wherein said travoprost particles are a mixture of travoprost and a biodegradable polymer consisting of a polylactide having an ester end group and an inherent viscosity specification from about 0.45 dl / g to about 0.85 dl / g, such as about 0.55 dl / g to about 0.75 dl / g, as measured at 0.1% w / v in chloroform at 25°C. In some of these embodiments, said travoprost particles comprise about 41 wt-% to about 45 wt-%, such as about 42 wt-% to about 44 wt-% or about 43 wt-%, travoprost based on the total mass of the travoprost particles. In some of these embodiments, said 25 travoprost particles comprise about 39 wt-% to about 43 wt-%, such as about 40 wt-% to about 42 wt-% or about 41 wt-%, travoprost based on the total mass of the travoprost particles. In some of these embodiments, the particle size distribution of said travoprost particles as determined by laser diffraction is characterized as follows: D10 of about 4 pm to about 6 pm, D50 of about 8 pm to about 10 pm, and D90 of about 14 pm to about 16 pm. In some of these embodiments, the particle size distribution of the travoprost particles as determined by laser diffraction is 30 characterized as follows: DIO of about 5 pm, D50 of about 9 pm, and D90 of about 15 pm. In some of these embodiments, the particle size distribution of said travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 5 pm to about 7 pm, D50 of about 12 pm to about 14 pm, and D90 of about 24 pm to about 26 pm. In some of these embodiments, the particle size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: D10 of about 6 pm, D50 of about 13 pm, and D90 of 35 about 25 pm. [000169] In some embodiments, the intracameral implant comprises a blend of different types of travoprost particles as described herein. In some embodiments, the Intracameral implant comprises a blend of only two types of travoprost particles as described herein. In some embodiments, the intracameral implant comprises a blend of only three types of travoprost particles as described herein. In some embodiments, the intracameral implant comprises a 5 blend of only four types of travoprost particles as described herein. [000170] In some embodiments, as described above, the travoprost particles are obtained by or obtainable by a process comprising a membrane emulsification step. fitodegradabte hydroQel [000171] In the intracameral implants of the present disclosure the biodegradable hydrogel comprises a 10 polymer network comprising one or more units of polyalkylene glycol and the travoprost particles are dispersed within the biodegradable hydrogel. [000172] In some embodiments, the polymer network comprises one or more units of polyethylene glycol. [000173] In some embodiments, the polymer network comprises one or more units of polyethylene glycol being cross-linked including a group represented by the following formula: nVp 15- wherein m Is 1, 2,3, and / or 6. in some embotfiments, m Is 1. In some embodiments, m Is 2. In some embodiments, m is 3. In some embodiments, m is 2 and 6. In some embodiments, m is 6. [000174] In some embodiments, the polymer network comprises one or more units of a multi-arm polyethylene glycol. 20 [000175] Multi-arm PEG units with a specified molecular weight as used herein may be abbreviated in the form of e.g. 8al5kPEG, referring to an 8-arm PEG with a molecular weight of 15,000 Daltons. In a 4-arm PEG, each of the arms may have an average arm length (or molecular weight) of the total molecular weight of the PEG divided by 4. A 4a20kPEG precursor thus has 4 arms with an average molecular weight of about 5,000 Daltons each. An 8a20k PEG precursor, which could also be used in combination with the 4a20kPEG precursor in the present 25 disclosure, thus has 8 arms each having an average molecular weight of 2,500 Daltons. Longer arms may provide Increased flexibility as compared to shorter arms. PEGs with longer arms may swell more as compared to PEGs with shorter arms. A PEG with a lower number of arms also may swell more and may be more flexible than a PEG with a higher number of arms. In addition, longer PEG arms have higher melting temperatures when dry, which may provide more dimensional stability during storage. [000176] In some embodiments, the polymer network comprises one or more units of a multi-arm polyethylene glycol having from 2 to 10 arms or from 4 to 8 arms. In some embodiments, the polymer network comprises one or more units of a multi-arm polyethylene glycol having 4 arms or 8 arms, such as 8 arms. In some embodiments, the polymer network comprises one or mare units of two different multi-arm polyethylene glycols, such as one multi-arm polyethylene glycol having 4 arms and one multi-arm polyethylene glycol having 8 arms. Also a combination of two different multi-arm polyethylene glycols both having 8 arms might be applied. [000177] In some embodiments, the multi-arm polyethylene glycol has an average molecular weight (such as a mass average molecular weight) from about 10,000 Da to about 20,000 Da or from about 12,500 Da to about 17,500 Da. In some embodiments, the multi-arm polyethylene glycol has an average molecular weight of about 15,000 Da. [000178] In some embodiments, the mufti-arm polyethylene glycol has a number average molecular weight (Mn) ranging from about 5 KDa to about 40 KDa, from about 5 KDa to about 30 KDa, from about 10 KDa to about 50 KDa, from about 10 KDa to about 40 KDa, from about 10 KDa to about 30 KDa, from about 10 KDa to about 20 KDa, from about 30 KDa to about 50 KDa, from about 35 KDa to about 45 KDa, from about 15 KDa to about 30 KDa, or from about 15 KDa to about 25 KDa. In some embodiments, the multi-arm polyethylene glycol has a number average molecular weight (Mn) of at least about 5 KDa, at least about 10 KDa, at least 15 about KDa, at least 20 about KDa, at least 30 about KDa, at least 40 about KDa, about 10 KDa, about 15 KDa, about 20 KDa, or about 40 KDa. [000179] The molecular weight of polyethylene glycol and polyethylene glycol derivatives can be determined by several methods, including gel electrophoresis such as SDS-PAGE (sodium dodecyl sulphate-polyacrylamide gel electrophoresis), gel permeation chromatography (GPC), GPC with dynamic light scattering (DLS) as well as Matrix-assisted laser desorption / ionization-time of flight (MALDI-TOF) spectrometry. The molecular weight of polyethylene glycol precursors as disclosed herein can be determined by any method known to the person of ordinary skill in the art, including SDS-PAGE, GPC and MALDI-TOF, and in particular is determined by GPC using a PEG standard of known molecular weight (determined e.g. by MALDI-TOF) and polydispersity (determined e.g. by GPC). In case a high accuracy is needed, MALDI-TOF can be used. [000180] In some embodiments, the polymer is formed by reacting an electrophilic group-containing multiarm polyethylene glycol precursor with a nucleophilic group-containing cross-linking agent. [000181] In some embodiments, the nucleophilic group Is an amine or a thiol. In some embodiments, the nucleophilic group is an amine. In some embodiments, the nucleophilic group-containing cross-linking agent has a molecular weight below 1,000 Da and comprises two or more primary aliphatic amine groups. In some embodiments, the nucleophilic group-containing cross-linking agent is a dilysine, trilysine, tetralysine, ethylenediamine, 1,3- diaminopropane, 1,3- diaminopropane, diethylenetriamine, or trimethylhexamethylenediamine. In some embodiments, the nucleophilic group-containing cross-linking agent is a trilysine, such as a salt of trilysine, such as trilysine acetate. [000182] In some embodiments, the polymer network of the biodegradable hydrogel in the intracameral implants of the present disclosure has the formula: wherein n represents an ethylene oxide repeating unit and the wavy lines represent the points of repeating units of the polymer network. In alternative embodiments, the polymer network of the biodegradable hydrogel In the ..... intracameral implants has the formula set forth above, but with an 8-arm PEG scaffold. [000183] in some embodiment, the polymer network is formed by reacting a one or more units of 10 polyethylene glycol (PEG) selected from 4a20K PEG SAZ, 4a20K PEG SAP, 4a20K PEG SG, 4a20K PEG SS, 8a20K PEG SAZ, 8a20K PEG SAP, 8a20K PEG SG, and 8a20K PEG SS ..... [000184] In some embodiments, the nucleophilic group-containing crosslinking agent is selected from the group consisting of 4a20K PEG NH2, 8a20K PEG NH2, and a trilysine. [000185] In some embodiments, the polymer network is amorphous (e.g., under aqueous conditions such as 15 in vivo}. In some embodiments, the polymer network is semi-crystalline (e.g., in the absence of water). [000186] In some embodiments, the implant is labeled by a visualization agent. In some embodiments, nucleophilic group-containing cross-linking agent is a trilysine and the trilysine is labeled with a visualization agent. In some embodiments, the visualization agent is selected from the group consisting of a fluorophore such as fluorescein, rhodamine, coumarin, and cyanine. In some embodiments, the nucleophilic group-containing crosslinking agent is fluorescein-conjugated trilysine. In some embedments, the fluorescein-conjugated trilysine is obtained by reacting trilysine acetate with N-hydroxysuccinimide (NHS)-fluorescein. In some embodiments, the trilysine is labeled by partial conjugation with the visualization agent. In embodiments wherein the implant comprises a visualization agent, such as fluorescein, the implant can be monitored in an eye in which it is inserted. [000187] In some embodiments, the implant does not comprise a visualization agent e.g. the trilysine is not labeled witha visualization agertt. [000188] In some embodiments, the electrophilic group is succinimidyl glutarate (SG), succinimidyl succinate (SS), succinimidyl carbonate (SC), succinimidyl adipate (SAP), and / or succinimidyl azelate (SAZ). In some embodiments, the electrophilic group is succinimidyl azelate (SAZ) and succinimidyl glutarate (SG). In some embodiments, the electrophilic group is succinimidyl azelate (SAZ). [000189] In some embodiments, the polyethylene glycol precursor has from 2 to 10 arms or from 4 to 8 arms. In some embodiments, the polyethylene glycol precursor has 4 arms or 8 arms, such as 8 arms, In some embodiments, two different polyethylene glycol precursors are applied, such as one polyethylene glycol precursor having 4 arms and one polyethylene glycol precursor having 8 arms. Also a combination of two different multi-arm polyethylene glycol precursors both having 8 arms might be applied. [000190] In some embodiments, the multi-arm polyethylene glycol in the multi-arm polyethylene glycol precursor has an average molecular weight (such as a mass average molecular weight) from about 10,000 Da to about 20,000 Da or from about 12,500 Da to about 17,500 Da. In some embodiments, the multi-arm polyethylene glycol in the multi-arm polyethylene glycol precursor has an average molecular weight of about 15,000 Da. [000191] in some embodiments, W electrophilic grwp-contaW^ polyethylene glycol precursor is 8-arm-15K-PEG-SG. In some embodiments, the electrophilic group-containing multi-arm polyethylene glycol precursor Is 8-arm-15K-PEG-SAZ and 8-arm-15K-PEG-SG [000192] In some embodiments, the electrophilic group-containing multi-arm polyethylene glycol precursor is 8-arm-15K-PEG-SAZ. [000193] In some embodiments, the electrophilic group-containing multi-arm polyethylene glycol precursor is 8-arm-15K-PEGSAZ and the nucleophilic group-containing cross-linking agent is a trilysine, such as a salt of trilysine, such as trilysine acetate. [000194] In sortie embodiments, the electrophilic group-containing multi-arm polyethylene glycol precursor is an NHS dicarboxylic acid ester-terminated multi-arm PEG precursor that can be represented by the formula: wherein n is determined by the molecular weight of the respective PEG-arm, m Is an integer from 0 to 10, and specifically is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10, and x is the number of arms (and thus can e.g. 2, 4, 8, etc., see above). 5- Where m is 1, each arm is terminated with a succinimidylsuccinate (SS) end group, where m is 2, each arm is terminated with a succinimidylglutarate (SG) group, where m is 3, each arm is terminated with a succinimidyladipate (SAP) group, and where m is 6, each arm is terminated with a succinimidylazelate (SAZ) group. With these specific electrophilic end groups, multi-arm PEG units may be abbreviated in the form of e.g. 4a20kPEG-SAP, referring to a 4-arm PEG with a succinimidyladipate end group and a molecular weight of 20,000. In the above formula, R Is a core 10 structure appropriate to provide the desired number of arms. For 4-arm PEG units and precursors, R can be a pentaerythritol structure, whereas for 8-arm PEG units and precursors, R can be a hexaglycerol structure. [000195] A reaction of an amine-containing crosslinker with activated ester-group containing PEG units results in a plurality of PEG units being crosslinked by the crosslinker via an amide group. In the case of PEGs with NHS-ester end groups such as succinimidylazelate (SAZ)-, succinimidyladipate (SAP)- or succinimidylgluatarate-(SG)-terminated 15 PEG units (see above), the reaction with amine group-containing crosslinkers result in a plurality of PEG units being crosslinked by the crosslinker via a hydrolyzable linker having the formula: . U 0 Q wherein m is an integer from 0 to 10, and specifically is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. For a SAZ-end group, m would be 6. For a SAP-end group, m would be 3. For a SG-end group, m would be 2. For an SS-end group, m would be 1. 20 [000196] In some embodiments, the weight ratio of the electrophilic group-containing multi-arm ......polyethylene glycol precursor to the nucleophilic group-containing cross-linking agent is from about 14:1 to about 18:1, or from about 15:1 to about 17:1. In some embodiments, the weight ratio of the electrophilic group-containing multi-arm polyethylene glycol precursor to the nucleophilic group-containing cross-linking agent is about 16:1. [000197] In some embodiments, the content of the biodegradable hydrogel with respect to the total weight 25 of the intracameral implant in its dried state is about 30 wt-% to about 50 wt-% or about 34 wt-% to about 42 wt- %, In so me embodiments, the content of the biodegradable hydrogel with respect to the total weight of the intracameral implant in its dried state is about 35 wt-% to about 45 wt-% or about 36 wt-% to about 40 wt-%. In some embodiments, the content of the biodegradable hydrogel with respect to the total weight of the intracameral implant in its dried state is about 37 wt-% to about 39 wt-% or about 38 wt-%. 5 [000198] In some embodiments, the total mass of -the biodegradable hydrogel fti the intracameral implant in its dried state Is about 30 pg to about 50 pg or about 34 pg to about 42 pg. In some embodiments, the total mass of the biodegradable hydrogel in the intracameral implant in its dried state is about 35 pg to about 45 pg or about 36 pg to about 40 pg. In some embodiments, the total mass of the biodegradable hydrogel in the intracameral implant in its dried state is about 37 pg to about 39 pg or about 38 pg. 10 [000199] In some embodiments, the content of the biodegradable hydrogel with respect to the total weight of the intracameral implant in its dried state is about 60 wt-% to about 80 wt-% or about 65 wt-% to about 75 wt-%. In some embodiments, the content of the biodegradable hydrogel with respect to the total weight of the intracameral implant in its dried state is about 67 wt-% to about 73 wt-% or about 68 wt-% to about 72 wt-%. In some embodiments, the content of the biodegradable hydrogel with respect to the total weight of the intracameral 15 implant in its dried state is about 69 wt-% to about 71 wt-% or about 70 wt-%. [000200] In some embodiments, the total mass of the biodegradable hydrogel in the intracameral implant in its dried state is about 230 pg to about 260 pg or about 235 pg to about 255 pg. In some embodiments, the total mass of the biodegradable hydrogel in the intracameral implant in its dried state is about 240 pg to about 250 pg or about 242 pg to about 248 pg. In some embodiments, the total mass of the biodegradable hydrogel in the 20 intracameral implant in its dried state is about 244 pg to about 246 pg or about 245 pg. [000201] In a further aspect, the present disclosure is also directed to a biodegradable hydrogel comprising a polymer network and travoprost particles being dispersed within said biodegradable hydrogel In this further aspect and corresponding embodiments thereof, the biodegradable hydrogel is not necessarily part of an intracameral implant. As regards the biodegradable hydrogel, the polymer network, and the travoprost partickes, reference is 25 made to the description above. For example, the polymer network may comprise 8-arm 15K PEG units. [000202] In a further aspect, the present disclosure is also directed to a biodegradable hydrogel comprising a polymer network and particles being dispersed within said biodegradable hydrogel, wherein the particles are a mixture of a prostaglandin analogue different to travoprost and a biodegradable polymer. The biodegradable hydrogel is not necessarily part of an intracameral implant. As regards the biodegradable hydrogel, the polymer 30 network, and the particles, reference is made to the description above. For example, in some embodiments the polymer network may comprise 8-arm 15K PEG units. Examples of prostaglandin analogues are latanoprost, tafluprost, bimatoprost, unoprostone, unoprostone isopropyl ester, and latanoprostene bunod. In some embodiments, the prostaglandin analogue is bimatoprost. In some embodiments, the prostaglandin analogue is latanoprost. In some embodiments, the prostaglandin analogue is tafluprost. Dimensions and further composition of the intracameral implant [000203] In some embodiments, the implant has a length of about l.SO mm to about 2.50 mm and a diameter of not more than 0.30 mm in its dried state. In some embodiments, the implant has a length of about 1.60 mm to about 2.40 mm or about 1.70 mm to about 2.30 mm in its dried state. In some embodiments, the implant has 5 a length of about 1.80 mm to about 2.20 mm or about 1.90 mm to about 2.10 mm in its dried state. In some embodiments, the implant has a length of about 1.95 mm to about 2.05 mm, such as about 2.00 mm, in its dried state. In some embodiments, the implant has a diameter of about 0.20 mm to about 0.30 mm or about 0.23 mm to about 0.29 mm in its dried state. In some embodiments, the implant has a diameter of about 0.24 mm to about 0.28 mm or about 0.25 mm to about 0.27 mm in its dried state. In some embodiments, the implant has a diameter of 10 about 0.25 mm, about 0.26 mm, or about 0.27 mm in its dried state. In some embodiments, the implant has a length of about 1.90 mm to about 2.10 mm and a diameter of about 0.24 mm to about 0.28 mm in its dried state. [000204] In some embodiments, the implant has a length of about 13.00 mm to about 16.00 mm and a diameter of not more than 0.20 mm in its dried state. In some embodiments, the implant has a length of about 14.00 mm to about 15.00 mm in its dried state. In some embodiments, the implant has a diameter of about 0.10 mm 15 to about 0.20 mm or about 0.15 mm to about 0.20 mm in its dried state. In some embodiments, the implant has a diameter of about 0.16 mm to about 0.18 mm or about 0.17 mm in its dried state. [000205] In some embodiments, the content of travoprost with respect to the total weight of the intracameral implant in its dried state is about 10 wt-% to about 40 wt-% or about 15 wt-% to about 35 wt-%. [000206] In some embodiments, the content of travoprost with respect to the total weight of the 20 intracameral implant in its dried state is about 20 wt-% to about 30 wt-% or about 25 wt-% to about 30 wt-%. In some embodiments, the content of travoprost with respect to the total weight of the intracameral implant in its dried state is about 22 wt-% to about 30 wt-% or about 24 wt-% to about 28 wt-% of travoprost. In some embodiments, the content of travoprost with respect to the total weight of the intracameral implant in its dried state is about 25 wt-% to about 27 wt-% or about 26 wt-%. 2.5- [000207] In some embodiments, the content of travoprost with respect to the total weight of the intracameral implant in its dried state is about 2 wt-% to about 22 wt-% or about 4 wt-% to about 20 wt-%. In some embodiments, the content of travoprost with respect to the total weight of the intracameral implant in its dried state is about 7 wt-% to about 17 wt-% or about 10 wt-% to about 14 wt-%. In some embodiments, the content of travoprost with respect to the total weight of the intracameral implant in its dried state is about 11 wt-% to about 13 30 wt-% or about 12 wt-% of travoprost. [000208] In some embodiments, the implant comprises a dose of about 5 pg to about 50 pg or about 10 pg to about 45 pg of travoprost. In some embodiments, the implant comprises a dose of about 10 pg to about 40 pg or about 15 pg to about 35 pg of travoprost. In some embodiments, the implant comprises a dose of about 20 pg to about 30 pg or about 25 pg to about 30 pg of travoprost. In some embodiments, the implant comprises a dose of about 22 pg to about 30 pg or about 24 pg to about 28 pg of travoprost. In some embodiments, the implant comprises a dose of about 25 pg to about 27 pg or about 26 pg of travoprost. [000209] In some embodiments, the implant comprises a dose of about 30 pg to about 50 pg or about 35 pg 5 to about 45 pg of travoprost. In some embodiments, the implant comprises a dose of about 36 pg to about 44 pg or about 37 pg to about 43 pg of travoprost. In some embodiments, the implant comprises a dose of about 38 pg to about 42 pg or about 39 pg to about 41 pg of travoprost. In some embodiments, the implant comprises a dose of about 40 pg of travoprost. [000210] In so m e embodiments, the implant is in the form of a fiber. 10 [000211] In some embodiments, the implant has a total weight of about 50 pg to about 150 pg, or of about 75 pg to about 125 pg in its dried state. In some embodiments, the implant has a total weight of about 80 pg to about 120 pg or of about 90 pg to about 110 pg in its dried state. In some embodiments, the implant has a total weight of about 95 pg to about 105 pg in its dried state. In some embodiments, the implant has a total weight of about 100 pg in its dried state. 15 [000212] In some embodiments, the implant has a total weight of about 300 pg to about 400 pg, or of about 320 pg to about 380 pg in its dried state. In some embodiments, the implant has a total weight of about 330 pg to about 370 pg or of about 340 pg to about 360 pg in its dried state. In some embodiments, the implant has a total weight of about 345 pg to about 355 pg in its dried state. In some embodiments, the implant has a total weight of about 350 pg in its dried state. 20 [000213] In some embodiments, the content of the biodegradable polymer with respect to the total weight of the intracameral implant in its dried state is about 29 wt-% to about 39 wt-% or about 31 wt-% to about 37 wt-%. In some embodiments, the content of the biodegradable polymer with respect to the total weight of -the intracameral implant in its dried state is about 32 wt-% to about 36 wt-% or about 33 wt-% to about 35 wt-% or about 34 wt-%. [000214] In some embodiments, the content of the biodegradable polymer with respect to toe total weight of 25 the intracameral implant in its dried state is about 10 wt-% to about 20 wt-% or about 12 wt-% to about 18 wt-%. In some embodiments, the content of the biodegradable polymer with respect to the total weight of the intracameral Implant in its dried state is about 13 wt-% to about 17 wt-% or about 14 wt-% to about 16 wt-% or about 15 wt-%. [000215] In some embodiments, the total mass of the biodegradable polymer in the implant in its dried state is about 29 pg to about 39 pg or about 31 pg to about 37 pg. In some embodiments, the total mass of the biodegradable 30 polymer in the implant in its dried state is about 32 pg to about 36 pg or about 33 pg to about 35 pg or about 34 pg. [0002161 In some embodiments, the total mass cf the biodegradable polymer in the implant in its dried state is about 47 pg to about 57 pg or about 49 pg to about 55 pg. In some embodiments, the total mass of the biodegradable polymer in the implant in its dried state is about 50 pg to about 54 pg or about 51 pg to about 53 pg or about 52 pg. [000217] In some embodiments, the content of travoprost with respect to the total weight of the intracameral implant in its dried state is about 11 wt-% to about 13 wt-%, such as about 12 wt-%, and the content of the 5 biodegradable polymer with respect to the total weight of the intracameral implant in its dried state is about 14 wt-% to about 16 wt-%, such as about 15 wt-%, wherein optionally the implant has a total weight of about 340 pg to about 360 pg, such as about 350 pg in its dried state. In some of these embodiments, the implant has a length of about 14.00 mm to about 15.00 mm and a diameter of about 0.15 mm to 0.20 mm in its dried state. [000218] In some embodiments, the implant comprises a dose of about 39 pg to about 41 pg, such as about 10 40 pg, of travoprost, and the total mass of the biodegradable polymer in the implant in its dried state is about 51 pg to about 53 pg, such as 52 pg, wherein optionally the implant has a total weight of about 340 pg to about 360 pg, such as about 350 pg in its dried state. In some of these embodiments, the implant has a length of about 14.00 mm to about 15.00 mm and a diameter of about 0.15 mm to 0.20 mm in its dried state. [000219] In some embodiments, the content of travoprost with respect to the total weight of the intracameral 15 implant in its dried state is about 24 wt-% to about 25 wt-%, such as about 26 wt-%, and the content of the biodegradable polymer with respect to the total weight of the intracameral implant in its dried state is about 33 wt-% to about 35 wt-%, such as about 34 wt-%, wherein optionally the implant has a total weight of about 90 pg to about 110 pg, such as about 100 pg in its dried state. In some of these embodiments, the implant has a length of about 1.90 mm to about 2.10 mm (such as about 2.00 mm) and a diameter of about 0.20 mm to 0.30 mm in its dried state. 20 [000220] In«me embodiments, ttie implant comprises a dose of atxwt 24 pg to about 26 pg, such as about 26 pg, of travoprost, and the total mass of the biodegradable polymer in the implant in its dried state is about 33 pg to about 35 pg, such as 34 pg, wherein optionally the implant has a total weight of about 90 pg to about 110 pg, such as about 100 pg in its dried state. In some of these embodiments, the implant has a length of about 1.90 mm to about 2.10 mm (such as about 2.00 mm) and a diameter of about 0.20 mm to 0.30 mm in its dried state. 25 [000221] In some embodiments, the intracameral implant further comprises a phosphate component. In some embodiments, the implant further comprises sodium phosphate. [000222] In some embodiments, the Implant comprises from about 1 pg to about 15 pg or from about 2 pg to about 13 pg sodium phosphate. In some embodiments, the implant comprises from about 1 pg to about 3 pg, such as about 2 pg, sodium phosphate. In some embodiments, the implant comprises from about 10 pg to about 14 30 pg, such as from about 11 pg to about 13 pg, sodium phosphate. In some embodiments, the implant comprises about 12 pg sodium phosphate. In some of these embodiments, sodium phosphate is present as sodium phosphate monobasic and sodium phosphate dibasic. [000223] In some embodiments, the content of sodium phosphate with respect to the total weight of the intracamera! implant in its dried state is about 1 wt-% to about 3 wt-%, such as about 2 wt-%. In some embodiments, the content of sodium phosphate with respect to the total weight of the intracameral implant in its dried state is about 3 wt-% to about 5 wt*%, such as about 4 wt-%. In some of these embodiments, sodium phosphate is present as Sodium phosphate monobasic arid sodium phosphate dibasic, [000224] In some embodiments, the travoprost sustained release biodegradable intracamera! implant comprising a biodegradable hydrogel and travoprost particles has the following composition in its dried state: • about 35 pg to about 45 pg, such as about 40 pg, travoprost; « about 240 pg to about 250 pg, such as about 245 pg, biodegradable hydrogel formed by reacting 8al5K PEG SAZ with trilysine acetate, optionally at a weight ratio of about 16:1; ♦ about 50 pg to about 55 pg, such as about 52 pg, biodegradable polymer, optionally wherein the biodegradable polymer consists of pqiy(D,L)lactWe* » optionally about 5 pg to about 7 pg, such as about 6 pg, sodium phosphate monobasic; and • further optionally about 6 pg to about 8 pg, such as about 7 pg, sodium phosphate dibasic., wherein the impiant has a total weight of about 340 pg to about 360 pg, such as about 350 pg, in its dried state. In some of these embodiments, toe median diameter of the travoprost particles is about 8 pm to about 13 pm> In some of these embodiments, the implant comprises only one type, of travoprost particles. In some of these embodiments, the biodegradable polymer consists of poiylactide (such as poly(DL)lactide) having an inherent viscosity specification from about 0.50 di / g to about 1.10 di / g, such as about 0,60 dl / g to about 1.00 dl / g, as measured at Q.5% w / v chloroform at 30°C, and optionally has an acid end group. In some of these embodiments, the biodegradable polymer consists of polylactide (such as poly(DL)lactide) having an Inherent viscosity specification from about 0.45 dl / g to about 0.85 dl / g, such as about 0.55 dl / g to about 8.75 di / g, as measured at 0.1% w / v chloroform at 25°C, and optionally has an ester end group. [000225] In some embodiments, the travoprost sustained release biodegradable intracamerai implant comprising a biodegradable hydrogel and travoprost particles has the foltowing composition in Its dried state: ♦ about 20 pg to about 30 pg, such as aixv / i 26 pg, travoprost; » about 35 pg to about 45 pg, such as about 38 pg, biodegradable hydrogel formed by reacting 8al5K PEG SAZ with trilysine acetate, optionally at a weight ratio of about 16:1; * about 30 pg to about 40 pg, such as about 34 pg, biodegradable polymer, optionally wherein the biodegradable polymer consists of pdy(D,L)lactlde; • optionally about 0.5 pg to about 1.5 pg, such as about 1 pg, sodium phosphate monobasic; and * further optionally about 0.5 pg to about 1.5 pg, such as about 1 pg, sodium phosphate dibasic, 5 wherein the implant has a total weight of about 90 pg to about 110 pg, such as about 100 pg, in its dried state, and optionally wherein toe implant has a length of about 1.50 mm to about 2.50 mm, such as about 2.00 mm, and a diameter of not more than 0.30 mm in its dried state. In some of these embodiments, the median diameter of toe travoprost particles is about 8 pm to about 13 pm. In some of these embodiments, the implant comprises only one type of travoprost partides. In some of these 10 embodiments, the biodegradable polymer consists of polylactide (such as polyCDlJIacMe) having an inherent viscosity specification from about 0.50 dl / g to about 1.10 di / g, such as about 0.60 dl / g to about 1.00 dl / g, as measured at 0.5% w / v chloroform at 30°C, and optionally has an add end group. In some of these embodiments, the biodegradable polymer consists of polylactide (such es poly(DL)lactide) having an inherent viscosity specification from about 0.45 di / g to about 0.85 dl / g, such as about 0.55 dl / g to about 0.75 dl / g, as measured at 0.1% w / v i 5 chloroform at 25eC, and optionally has an ester end group. [000226] In some embodiments, the implant has a composition according to Table 8 of the present disclosure. In some embodiments, the implant has a composition according to Table 11 of the present disclosure. Io. pfe? release Btopertles of toe intracamerai imalant [000227] In some embodiments, the implant shows a travoprast in vitro release of less than about 60% or 20 less than about 25% or less than about 20% based on the total weight of travoprost in the intracameral implant after incubating the Intracameral implant for 1 day under simulated physiological sink conditions in 50 ml of lx PBS, 0,5% castor oil, 0.01% sodium fluoride buffer at pH 7.2-7.4 at 37 °C (initial burst). [000228] In some embodiments, the implant shows a travoprost in vitro release of about 40% to about 60% or of about 1.0% to about 30% or of about 15% to about 25% based on the total weight of travoprost in the 25 intracameral implant after incubating the intracameral implant for 1 day under simulated physiological sink conditions in 50 ml of lx PBS, 0.5% castor oil, 0.01% Sodium fluoride buffer at pH 7.2-7,4 at 37 °C (initial burst}. [000229] In some embodiments, the implant shows a travoprost tn vitro release of about 10% to about 25% or about 10% to about 20% based on the total weight of travoprost in the intracameral implant after incubating the intracameral implant for 1. day under simulated physiological sink conditions in 50 ml of lx PBS, 0,5% castor oil, 30 0.01% sodium fluoride buffer at pH 7.2-7.4 at 37 °C, [000230] In some embodiments, the implant shows a travoprost fo wto release of less than about 50% or less than about 40% or less than about 30% based on the total weight of travoprost in the intracameral implant after incubating the intracameral implant for 20 days under simulated physiological sink conditions in 50 ml of lx PBS, 0.5% castor oii, 0,01% sodium fluoride buffer at pH 7.2-7.4 at 37 °C. [Q00231] In some embodiments, the implant shows a travoprost in wtro release of about 20% to about 30% or of about 30% to about 40% or of about 40% to about 50% or of about 85% to about 95% based on the total weight of travoprost In the intracameral Implant after incubating the intracameral Implant for 20 days under simulated physiological sink conditions in 50 ml of lx PBS, 0,5% castor oil, 0.01% sodium fluoride buffer at pH 7.27.4 at 37 °C. [000232] In some embodiments, the implant shows a travoprost in vitro release of less than about 80% or less than about 70% or less than about 50%, based on the total weight of travoprost in the intracameral implant after incubating the intracameral implant for 40 days under simulated physiological sink conditions, in 50 rat. of lx PBS, 0.5% castor oil, 0.01% sodium fluoride buffer at pH 7.2-7.4 at 37 °C. [000233] In some embodiments, the implant shows a travoprost fo vitro release of about 40% to about 50% Or of about 60% to abbot 70% based on the total weight of travoprost in the intracameral implant after Incubating the intracameral implant for 40 days under simulated physiological sink conditions in 50 ml of lx PBS, 0.5% castor oil, 0.01% sodium fluoride buffer at pH 7.2-7,4 at 37 °C. [000234] In some embodiments, the implant shows a travoprost in vitro release of less than about 80% or less than about 70% based on the total weight of travoprost in the intracameral implant after incubating the intracameral implant for 60 days under simulated physiological sink conditions in. 50 mL of lx PBS, 0.5% castor oil, 0,01% sodium fluoride buffer at pH 7,2-7.4 at 37 °C, [000235] In some embodiments, the implant shows a travoprost in vitro release of about 55% to about 65% or of about 60% to about 70% or of about 70% to about 80% or of about 75% to about 85% or of about 85% to about 95% based on toe total weight of travoprost in the intracameral implant after incubating toe intracameral implant for 60 days under simulated physiological sink conditions in 50 mt of lx PBS, 0.5% castor oil, 0.01% sodium fluoride buffer at pH 7,2-7.4 at 37 °C. [000236] In some embodiments, the implant shows a travoprost in vitro release of less than about 100% or less than about 90% based on the total weight of travoprost In the intracameral implant after incubating the Intracameral implant for 80 days under simulated physiological sink conditions in 50 ml of lx PBS, 0.5% castor oil, 0.01% sodium fluoride buffer at pH 7.2 -7.4 at 37 °C, [000237] In some embodiments, the implant shows a travoprost in vitro release of about 75% to about 85% or of about 851% to about 95% based on the total weight of travoprost in the intracameral implant after incubating the intracameral implant for 80 days under simulated physiological sink conditions in 50 ml of lx PBS, 05% castor oil, 0.01% sodium fluoride buffer at pH 7.2-7.4 at 37 °C. [000238] in some embodiments, the implant shows a travoprost A? vitro release of less than about 100% or less than about 90% based on the total weight of travoprost in the intracameral implant after Incubating the intracameral implant far 100 days under simulated physiological sink conditions in 50 ml of lx PBS, 0.5% castor oil, 0.01% sodium fluoride buffer at pH 7.2-7.4 at 37 °C. [000239] In some embodiments, the implant shows a travoprost in vitro release of about 85% to about 95% based on the total weight of travoprost in the intracameral implant after incubating the intracameral implant for 100 days under simulated physiological sink conditions in 50 ml of lx PBS, 0.5% castor oil, 0.01% sodium fluoride buffer at pH 7.2-7.4 at 37 °C. [000240] In some embodiments, the % In vitro release of travoprost given in the above embodiments refers to an average travoprost release from about 10 to about 20 implants, such as about 10 or about 15 implants, examined. [000241] In some embodiments, the mean absolute deviation of the % in vitro release of travoprost given in the above embodiments is at most about 10% or at most about 5%. [000242] In some embodiments, the implant shows an essentially zero-order travoprost in vitro release profile when incubating the intracameral implant under simulated physiological sink conditions in 50 mL of lx PBS, 0.5% castor oil, 0.01% sodium fluoride buffer at pH 7.2-7.4 at 37 SC, optionally when Incubating the intracameral Implant for about 0.5 months or longer, or about 1 month or longer, or about 1.5 months or longer, or about 2 months or longer, or about 2.5 months or longer, or about 3 months or longer, or about 3.5' months or longer, or about 4 months (i.e, the essentially zero-order travoprost in vitro release lasts for about 0,5 months or longer, or about 1 month or longer, or about 1.5 months or longer, or about 2 months or longer, or about 2.5 months or longer, or about 3 months or longer, or about 3.5 months or longer, or about 4 months). [000243] In some embodiments, the Implant shows an essentially linear travoprost in vitrox^ea^. profile when incubating the intracameral implant under simulated physiological sink conditions in 50 mL of lx PBS, 0.5% castor oil, 0.01% sodium fluoride buffer at pH 7.2-7,4 at 37 °C, optionally when incubating the intracameral implant for about 0.5 months or longer, or about 1 month or longer, or about 1.5 months or longer, or about 2 months or longer, or about 2,5 months or longer, or about 3 months or longer, or about 3.5 months or longer, or about 4 months (Le. the essentially linear travoprost in vitro release lasts for about 0.5 months or longer, or about 1 month or longer, or about 1.5 months or longer, or about 2 months or longer, or about 2.5 months or longer, or about 3 months or longer, or about 3.5 months or longer, or about 4 months), [000244] in some embodiments, the travoprost in vitro release from the implant when incubating the Intracameral implant under simulated physiological sink conditions in 50 ml of lx PBS, 0.5% castor oii, 0.01% sodium fluoride buffer at pH 7.2-7.4 at 37 °C is essentially constant for a period of about 0.5 months or longer, or about 1 month or longer, or about 1.5 months or longer, or about 2 months or longer, or about 2.5 months or longer, or about 3 months or longer, or about 3,5 months or longer, or about 4 months, Method of manufacturing a travoprost sustained release biodegradable intracameral implant [QQG24S] In a further aspect, the present disclosure Is directed to a method of manufacturing a travoprost sustained release biodegradable intracameral impiant, the method comprising: -preparing or providing travoprost particles according to the present disclosure, -preparing a precursor mixture of an electrophilic group-containing multi-arm polyethylene glycol precursor and the travoprost partides, -crosslinking the precursor mixture using a nucleophilic group-containing crosslinking agent to form a polymer network, thereby obtaining a biodegradable hydragel comprising the polymer network, wherein the travoprost particles are dispersed in the biodegradable hydrogel, and -drying the biodegradable hydrogel to provide the implant. [000246] As regards further details of the travoprost particles prepared or provided in the method of manufacturing, reference Is made to the chapter “Travoprost particles" above.. For example, in some embodiments of the method of manufacturing a travoprost sustained release biodegradable intracameral implant, toe travoprost particles have a median diameter of about 2 pm to about 19 pm or of about 8 pm to about 13 pm as determined by laser diffraction. [000247] As regards further details of the electrophilic group-containg multi-arm polyethylene glycol precursor, reference is made to the section “Travoprost sustained release biodegradable intracameral implant" above. For example, in some embodiments of the method of manufacturing a travoprost sustained release biodegradable intracameral implant, the electrophilic group-containing multi-arm polyethylene glycol precursor is 8-arm-15K-PEG-SAZ. [000248] As regards further details of toe nucleophilic group-containg Crosslinking agent, reference is made to the section “Travoprost sustained release biodegradable intracameral implant" above. For example, in some embodiments of the method of manufacturing a travoprost sustained release biodegradable intracameral implant, the nucleophilic group-containg crosstoklng agent is a triiysme, such as trilysine acetate. [000249] In some embodiments, the precursor mixture of the electrophilic group-containing multi-arm polyethylene glycol precursor and the travoprost particies comprises a phosphate buffer, such as a sodium phosphate monobasic buffer. [000250] In some embodiments, the nucleophilic group-containing crosslinking agent is present in a phosphate buffer, such as a sodium phosphate dibasic buffer. [000251] in some embodiments, drying the hydrogel is carried out at about 30°C to about 35’C, such as at about 33°C. In some embodiments, drying is carried out under nitrogen Row. In some embodiments, drying is 5 carried out for about 48 to about 72 hours. In some embodiments, the biodegradable hydrogel is dried in a tubing. [000252] In some embodiments, the method further comprises loading the implant into an injection device for intracamerai injection of the implant. In some embodiments, the injection device Is a syringe. In some embodiments, the needle of the syringe is a 26G needle or a 27G needle. In some embodiments, the needle of the syringe is a 26G needle. In some embodiments, the needle of the syringe is a 27G needle. 10 [000253] In some embodiments, the method further comprises loading the implant into the needle of a syringe for intracamerai Injection of the implant, wherein the needle is a 26G or a 27G needle. [000254] in some embodiments, the method further comprises sterilizing the injection device (such as the syringe) loaded with the intracamerai implant, optionally wherein sterilization is carried out by gamma irradiation. [000255] In some embodiments, the method of manufacturing the intracamerai implant is described in 15 Example 2. [000255] in another aspect, the present disclosure is directed to a travoprost sustained release biodegradable intracamerai implant obtainable by or obtained by the method as described in this chapter ("Method of manufacturing a travoprost sustained release biodegradable implant"), Device for injection of the travoprost implant of the present disclosure and kit .20 [000257] In a further aspect, the present disclosure is directed to an injection device for intracamerai injection of an implant according to the present disclosure. In some embodiments, the injection device is loaded with a travoprost sustained release biodegradable intracamerai implant as defined in the section "Travoprost sustained release biodegradable intracamerai implant" above. In some embodiments, the injection device is a syringe. In some embodiments, the injection device Is a syringe with a 26G needle or a 27G needle, In some embodiments, the 25 injection device is a syringe with a 26G needle. In some embodiments, the injection device is a syringe and is loaded with the intracamerai implant In some embodiments, the injection device is a syringe, and the needle of the syringe is leaded with the intracamerai implant, wherein the needle is a 26G needle. [000258] In some embodiments, the injection device is a syringe as described in Example S and / or as shown in Figure 18. [000259] In a further aspect, the present -disclosure is directed to a kit comprising aft intracameral implant according to the present disclosure 0n particular, as defined in the section “Travoprost sustained release biodegradable intracameral implant" above) and art injection device for intracameral injection of the intracameral implant In some embodiments, the injection device is an injection device as described in this chapter ("Device tor injection of the travoprost implant of the present disclosure and kit"), in particular the injection device, is a syringe, Uses and further methods of the present disclosure [000260] In a further aspect, the present disclosure is directed to a method of treating an ocuiar disease in a subject in need thereof, the method comprising inserting an intracameral implant according to the present disclosure into an eye of the subject in need of treatment. As regards the intracameral implant, reference is made to the description above, in particular, to the chapter “Travoprost sustained release intracameral implant". [000261] in a further aspect, the present disclosure is directed to a method of treating glaucoma in a subject in need thereof comprising inserting an intracameral implant according to the present disclosure into an eye of the subject in need of treatment. As regards the intracameral implant, reference is made to the description above, in particular, to the chapter "Travoprost sustained release Intracameral implant", [900262] in a further aspect, the present disclosure is directed to a method of reducing the intraocular pressure in a subject with glaucoma comprising inserting an intracameral implant according to the present disclosure into an eye of the subject in need of treatment. As regards the intracameral implant, reference is made to the description above, in particular, to the chapter "Travoprost sustained release intracameral implant". [000263] In some embodiments, glaucoma is open angle giaucoma, optionally mild, moderate, or severe open angle glaucoma. [000264] In a further aspect, the present disclosure Is directed to a method of treating ocular hypertension in a subject in need thereof comprising inserting an Intracamera! implant according to the present disclosure into an eye of the subject in need of treatment. As regards the Intracameral implant, reference is made to the description above, in particular, to the chapter "Travoprost sustained release intracameral implant". [00G265] In a further aspect, the present disclosure is directed to a method of reducing the intraocular pressure in a subject with ocular hypertension comprising inserting an intracameral implant according to the present disclosure into an eye of the subject in need of treatment. As regards the intracameral implant, reference is made to the description above, in particular, to the chapter “Travoprost sustained release intracameral imptent", [000266] In some embodiments, the intracameral implant is Inserted within the Iridocorneal angle of the anterior chamber of the eye of the subject in need of treatment. [000267] In some embodiments, the method comprises inserting one single intracamera! implant per eye. In some embodiments, the method comprises bilateral treatment, Le. treatment of both eyes of a subject by inserting one single intracameral implant in each of the subject's eyes. [000268] In some embodiments, the treatment period with one single intracamerai implant is about 1 to about 24 months or about 3 to about 12 months. In some embodiments, the treatment period with one single intracameral implant is about 6 to about 12 months or about 8 to about 10 months. In some embodiments, the treatment period with one single intracameral implant is at least about 9 months. [000269] In some embodiments, the treatment period with one single intracameral implant is about 4 months or longer, or at least about 4 months. In some embodiments, the treatment period with one single intracameral implant is about 4 months. [000270] In some embodiments, after a first treatment period with a first intracameral implant at least once a new intracameral implant is inserted that provides for a further treatment period. In some embodiments, the new intracameral implant is an intracameral implant as described hemin. In some embodiments, the new intracameral implant is the same as the intracameral implant inserted for the prior treatment period. [000271] In some embodiments, treatment is repeated every year, twice a year, 3 times a year or four times a year in about equal time distances. [000272] In some embodiments, the treatment is continued until no further treatment is required. [000273] In some embodiments, the intracameral implant provides for a sustained release of travoprost into the aqueous humor. [000274] In some embodiments, the subject is a human. [000275] In a further aspect, the present disclosure is directed to the intracameral implant as described herein for use as a medicament. In a further aspect, the present disclosure is directed to the intracamerai implant as described herein for use in a method of treating or reducing Intraocular pressure as described in this chapter (“Uses and further methods of the present disclosure") above. As regards the intracamerai implant, reference is made to the description above, in particular, to toe chapter ’’Travoprost sustained release intracameral implant". [000276] In a further aspect, the present disclosure is directed to the use of ths intracamers! implant according to the present disclosure in the manufacture of a medicament. In a further aspect, the present disclosure is directed to the use of the intracameral implant according to the present disclosure in the manufacture of a medicament for a method of treating or reducing intraocular pressure as described in this chapter (“Uses and further methods of the present disclosure") above. As regards the intracameral implant, reference is made to the description above, in particular, to the chapter "Travoprost sustained release intracamerai implant". [000277] In a further aspect, the present disclosure is directed to a method of treating an ocular disease in a subject in need thereof comprising administering the travoprost particles according to the present disclosure into an eye of the subject in need of treatment. As regards the travoprost particles, reference is made to the description above, in particular, to the chapter "Travoprost particles’'. [000278] In a further aspect, the present disclosure is directed to a method of treating glaucoma in a subject in need thereof comprising administering the travoprost particles according to the present disclosure into an eye of the subject In need of treatment. As regards the travoprost particles, reference is made to the description above, in particular, to the chapter "Travoprost particles". [000279] In a further aspect, the present disclosure is directed to a method of reducing the intraocular pressure in a subject with glaucoma comprising administering the travoprost particles according to the present disclosure into an eye of the subject in need of treatment. As regards the travoprost particles, reference is made to the description above, in particular, to the chapter "Travoprost particles". [000280] In some embodiments, glaucoma is open angle glaucoma, optionally mild, moderate, or severe open angle glaucoma. [000281] In a further aspect, the present disclosure is directed to a method of treating ocular hypertension in a subject In need thereof comprising administering the travoprost particles according to the present disclosure into an eye of the subject in need of treatment. As regards the travoprost particles, reference is made to the description above, in particular, to the chapter "Travoprost particles". [000282] In a further aspect, the present disclosure is directed to a method of reducing the intraocular pressure in a subject with ocular hypertension comprising administering the travoprost particles according to the present disclosure into an eye of the subject: In need of treatment. As regards the travoprost particles, reference is made to the description above, in particular, to the chapter "Travoprost particles". [000283] In some embodiments, the subject is a human. [000284] In a further aspect, the present disclosure is directed to the use of the travoprost particles according to present disclosure in. the manufacture of a medicament. In a further aspect, the present disclosure is directed to the use of the travoprost particles according to the present disclosure in the manufacture of a medicament for a method of treating or reducing intraocular pressure as described in this chapter ("Uses and further methods of the present disclosure") above. As regards the travoprost particles, reference is made to the description above, In particular, to the chapter "Travoprost particles”. [GGG285] In a further aspect, the present disclosure is directed to the use of the travoprost particles according to the present disclosure in the manufacture of a travoprost sustained release biodegradable intracamera! implant. As regards the travoprost particles, reference is made to the description above, in particular, to the chapter "Travoprost particles". [000286] in a further aspect, the present disclosure is directed to the travoprost particles according to the present disclosure for use as a medicament. As regards the travoprost particles, reference is made to the description above, in particular, to the chapter "Travoprost partides". [000287] In a further aspect, the present disclosure is directed to the travoprost partides according to the present disclosure for use in a method of treating or reducing intraocular pressure as described In this chapter ("Uses and further methods of the present disclosure") above. As regards the travoprost particles, reference is made to the description above, in particular, to the chapter ’’Travoprost particles". [000288] According to certain embodiments of the present disclosure, the implant is in a dried state prior to insertion and becomes hydrated once inserted into the eye. In certain embodiments the hydration occurs in less than 2 minutes. [000289] In some embodiments, the intracameral implant when inserted into the anterior chamber of a human eye, such as within the iridocorneal angle (e.g. below Schwalbe’s line), shows limited movement. Without wishing to be bound to any theory', it is believed that the hydrogel implant when inserted into the anterior chamber of the eye swells sufficiently by taking up the aqueous humor and dwreby gets fixated in the iridocorneal angle and will therefore not move during its entire period of being placed there. During the period of treatment, the implant gets increasingly soft and, therefore, can adapt further to the anatomical conditions thereby further prohibiting any movement before the hydrogel fully degrades. [000290] In some embodiments, the intracameral implant is gentle to the endothelium. Without wishing to be bound to any theory, it is believed that the prohibition of movement and its soft tissue-lite texture provides for the implant's gentleness to the endothelium and overall safety of the implant and, therefore, allows repeated administration. It is further believed that due to the possibility of size decrease such implants are suitable for a wide range of anatomical conditions including narrow iridocorneal angles, [000291] In some embodiments, the intracameral implant when inserted into a human eye, such as within the iridocorneal angle, does not cause inconvenience or discomfort, such as a sensation of having a foreign object in the eye or eye pain. [000292] in some embodiments, the implant is cosmetically invisible. [000293] In some embodiments, the intracameral implant is biodegradable in a residual-free mariner once inserted into the anterior chamber of the subject's eye and does not need to be removed by a surgery, i.e. the implant is fully biodegradable. [000294] In Some embodiments, the intracameral implant of the present disclosure provides for a long-term treatment effect. [00029S] in some embodiments, repeated treatment of a subject is possible with the intracameral implants of the present disclosure. 5 [000296] In some embodiments, essentially no endothelial damage occurs foltowing administration of the intracameral implant. In some embodiments, essentially no no change in pachymetr / occurs following administration of the intracameral implant. In some embodiments, no change of endothelial cell count occurs in the trated eye during a treatment period and / or the entire treatment. In some embodiments, no change of the thickness of the cornea occurs in the trated eye during a treatment period and / or the entire treatment. 10 EXAMPLES [000297] The following Examples are included to demonstrate certain aspects and embodiments of fine disclosure as described in the claims. It should be appreciated by those of skill in the art, however, that the following description is illustrative only and should not be taken in any way as a restriction of the disclosure-. 15 EXAMPLE 1: MANUFACTURE OF TRAVOPROST-LOADED MICROPARTICLES [000298] Travoprost-loaded microparticles were produced by membrane emulsification in which a hydrophobic dispersed phase (DP) is passed through a membrane of defined pare size into a hydrophilic continuous phase (CP). As shown herein, membrane emulsification allows for a narrow particle size distribution as well as the 20 capability to fabricate microparticles of smaller diameter in higher yield as possible with other microparticle production processes, such as homogenization. [000299] Membrane emulsification may be performed using various systems. In the current Example, membrane emulsification was performed using the LDC-1 system by Mlcrapore Technologies (United Kingdom) or the AXF-Minf system by Micropore Technologies (United Kingdom). TheLDC-i (Micropore Technologies, United Kingdom) 25 and the AXF-Mim (Micropore Technologies, United Kingdom) are membrane emulsification systems that were applied to fabricate the travoprost microparticles with narrow particle size distribution in high yield. The LDC4 can be referred to as an academic test unit designed to be directly scalable to Micropore AXF units. [900300] The CP was a 1% w / w polyvinyl alcohol (PVA) solution in RODI water prepared by dilution of a 4% w / w PVA stock. PVA acts as emulsifier. Travoprost and poly (D,L-lactide) (PLA) were dissolved in dichtoramethafie 50 (DCM) to prepare the DP (single-phase solution). [000301] Microparticles were exemplarly produced with each of four types of PLA: 4A, 7A, 9A, and 5.5E ■when using the AXF-Mini system. The target PLA concentration in the DP was 35.0% w / v, while that of travoprost ranged from 25.9-29.1% w / v depending on the PLA type. [000302] Microparticles were exemplariy produced with each of three types of PLA: 4A, 9A and S.5E when using the LDC-1. The target travoprost loading was 50.0% w / v, while the PLA concentration in the DP ranged from 20.6 - 43.3% w / v depending on PLA type. [000303] The different molecular weight polymers are described as 4A, 7A, 9A and 5 St PLA, wherein the numerical value designates the target inherent viscosity (XV) of the polymer in chloroform which correlates to the PLA molecular weight and the letter suffix designates acid (A) or ester (E) end group. When measured in 0.5 % w / v 10 chloroform at 30 °C, 4A PLA has an inherent viscosity specification of 0.35 to 0.45 di / g; 7A PLA has an inherent viscosity specification of 0.60 to 0.80 and 9A PLA has an inherent viscosity specification of 0.80 to 1.00 dl / g. When measured in 0.1 % W / V chloroform at 25 *C, 5.5E PLA has an inherent viscosity specification of 0.55 to 0.75 dl / g. Parameters on how the inherent viscosity of polylachdes can be measured are set forth in Table 1 below. Table 1 Experimental parameters for measuring the inherent viscosity of the polyiactides. Varrabte | OKpanmentef setup Tor | Experimental setup for 5.5E 4A, 7 A and 9A PIA & j PLA t ester-terminated 1 acid-termmated polymers i polymers Concentration | 0.5 % w / v 1 0.1 % w / v Temperature 30 °C 1 25 °C Ubbetohde Viscometer Size OB OB Approximate Viscometer Constant (C) 0,005 mm^ / sz 0.005 mm’ / s’ Capillary Working Length (L) 40 mm 1 40 mm Buib Volume (V) 3.0 ml | 3.0 ml Capillary Inside Diameter (d) I 0.46 mm 0,46 mm Approximate flow time of solvent (CHCh) 1 78 S 78 s Production with AXF-Mini 15 [000304] Once the CP and DP were prepared., the AXF-Mini was set up for use. The AXF-Mini comprises a stainless insert and membrane that are held in the body of the AXF-Mini with stainless steel end caps tri-ciamps. The membrane Is cylindrical in shape with laser-cut pores etched into the center wails. The stainless-steel insert fits within the membrane and defines the distance between the inner diameter of the membrane and the outer diameter 20 of the insert; this region is where particle formation occurs. The CP inlet tubing enters the AXF-Mlni through the cylindrical membrane / insert, while the DP inlet enters perpendicularly through the membrane pores. [Q00305] The DP was injected via a syringe pump into a flowing stream of the CP. The injection occured immediately prior to passing through the AXF-Mini to disperse the DP Into nascent microparticles. The flow rate of the DP into the AXF-Mini was maintained at 0.25 mL / min, while the CP was set from 70-80 mL / min (smaller partide size diameter). Particles were produced as droplets of DP that were sheared off by the CP as they passed through the pores of the membrane. The particles, along with CP, exit the AXF-Mini and were collected in a beaker under an overhead mixer (stirred quench vessel). Once the DP injection was completed, the DP pump was turned off while the CP continued to run until the desired final quench volume was achieved (CP:DP ratio was 600:1 by volume). [000306] The resultant particles were stirred overnight in the quench vessel to harden the microparticles and extract and evaporate excess DCM. Once the particles had stirred for > 16 hours, they were cleaned and concentrated using tangential flow filtration (IFF). The cteaned particles were then lyophilized to remove all water and yield a dry powder, [000307] A schematic overview of the manufacturing process of the travoprost particles using AXF-Mini is given in Figure 1. Production with LDC-1 [000308] Once the CP and DP solutions are prepared, the LDC-1 is set up for use. The LDC-1 unit uses a circular membrane of defined pore size and a stirrer to introduce shear and form an oil-in-water emulsion of droplets that harden to form individual particles. PTFE tubing is secured to the barb of the LDC-1 base, while the other end of the tubing is secured to a barb-to-luer fitting for the syringe connection. A syringe containing the homogenous DP solution is affixed to a syringe pump, and the DP solution is primed Into the base of the LDC-1. The LDC-1 is comprised of a stainless-steel membrane that is seated in the base of the 1001 The membrane is a fiat disk in shape with laser-cut pores etched into a ring formation around the disk. A Viton sealing gasket is placed atop of the membrane and the sampling chamber Is threaded into the base until maximum hand tightness. The sampling chamber is filled with CP solution before the stirrer blade (attached to the LDC-1 cap) is secured in place. The overhead .stirrer creates the shear in the system., and the speed at which it rotates is dependent on the agitation setpoint. The shear from the overhead stirrer generates the discrete particles as the DP passes through the pores in the membrane. [000309] A membrane with 5 pm pores was utilized while the flow rate of the DP solution into the LDC-1 was maintained at Q. 125 mL / mfn, and the agitation setpoint far the overhead stirrer was maintained at 18V. 3mL of DP solution was injected into the LDC-1 sampling chamber to maintain a 54:1 CP:DP ratio by volume. Once the injection was complete, the overhead stirrer was removed from the LDC-1 and the nascent micropartictes were transferred into a beaker, under another overhead stirrer, containing CP solution to allow the microparticles to quench at a 600:1 CP:DP ratio by volume. The resultant microparticles were stirred at 230 RPM overnight, under a nitrogen sweep across the beaker headspace, to harden and remove excess DCM by evaporation, Once the microparticles have been quenched for 18 - 24 hours, they were cteaned from the CP solution and concentrated using centrifugal methods. The cleaned microparticles were then, lyophilized to remove ail water and yield a dry powder. [000310] Once the micropartides produced using the LDC-1 or AXF-Mini, respectively,. were dried, they were imaged by scanning electron microscope (SEM), particle size distribution was determined by taser diffraction, and the travoprost content was determined. A schematic overview of the resultant travoprost particles is shown in Figure 2. Laser diffraction [000311] The particle size distribution (PSD) was measured by laser diffraction using a Malvern Mastersizer 3D00E. The Mastersizer was set up by first initializing the software and selecting Manual Measurement. PLA microparticles were measured with the settings shown in Table 2. 10 Table 2 Parameters for particle size distribution (PSD) measurement. Particle Type Spherical Material Name PLA Refractive Index 1.4589 Density (g / cm3) 1 Dispersant Water Background Measurement Duration (s) 10 Sample Measurement Duration (s) 10 Number of Measurements 10 Delay between Measurements fo) 2 Pre-measurement Delay (s) 0 Pre-alignment Delay (s) a Obscuration Lower Limit (%) 0.1 Obscuration Higher Limit (%) 20 Analysis Model General: purpose Result Type Volume Distribution [000312] Once settings were confirmed, the small volume sample dispersion unit was filled with RODI water. The dispersion unit controller was set to ^1000 rpm. On the screen, the laser measured the obscuration at -75%. The system was then initialized, and background signal was removed, resulting in an obscuration reading of 0%. The microparticle test sample was prepared for analysis by adding ~.5 mg of microparticles to a 2 ml Eppendorf tube i 5 and filling with RODI water. The tube was vortexed to suspend the particles. The sample was then transferred to the small volume sample dispersion unit using a disposable transfer pipette. Sample was added until the obscuration reads ~5-10%, 10 sample measurements were then token and DIO, D50, D90, and D99 (pm) were reported. Microparticles produced bv AXFMtni [000313] Exemplary formulation and process parameters for the AXF-Mini to yield particles of smaller 20 diameter are summarized in Table 3 betew. The resultant particles had a particle size distribution of DiO - 4.61 pm; D50 = 7.89 pm; DOO = 12.84 pm as measured by a Malvern Mastersizer 3000E as outlined above. Table 3 Example formulation and process parameters to yield small diameter particles. Microparticle Lot: MS-618078. Formulation Parameters Continuous Phase (CP) PVA 1% w / w Water QS Dispersed Phase (DP) 7APLA 34.9% w / v Travoprost load* 47.3% DCM QS AXF-Mmi Process Parameters CP How rate 80 mMmin DP flow rate 0.25 ml / min Membrane size 5 pm Insert size 9.9 mm Particle S»e Distribution DIO 4.61 um D50 / .89 pm DM 12.84 gm * I ravoprost load = (amount of travoprost) / [(amount of travoprost) + (amount of PLA)] QS ~ quantity sufficient. Ui [00Q314] .Further microparticles were prepared by membrane emulsification (AXF-Mini) as described above. Sfee Table 4 for further details. Tabi® 4 Information on different travoprost particles produced by AXF-Minl (including specific microparticle lot number). Microparticle Lot Description i DIG (pm) D50 (pm) D90 (pm) Travoprost Content (%w / w) 1 M P-595-078 4A Microparticles i 4.5 8.7 14.3 45.5 MS-618-07S 7 a H.autwrtiues 5 <0 79 12.8 423 MP-695-082 9A Microparticles Hi ^7.9 43 3 M P-695-097 5.5E Microparticles 5.0 h.s 15.4 47 <i travoprost content is per formulation notebook record, not measured. Given on dry basis of final microparticles. 10 [00031$] The particle size distribution (PSD) of travoprost-loaded microparticles comprising 4A PLA (Lot No. ■MP-695-G78) is shown in Figure 3. Corresponding scanning electron microscopy (SEM) images of the travoprost-loaded microparticles comprising 4A PLA are shown tn Figure 4A. [000316] The particle size distribution (PSD) of travoprost-loaded mfcroparticfes comprising 7A PLA (Lot No. MP-618-078) is shown in Figure 5. Corresponding scanning electron microscopy (SEM) images of the travoprast-loaded microparticles comprising 7A PLA are shown in Figure 6A [000317] The partide size distribution (PSD) of travoprost-loaded micropartides comprising 9A PLA (Lot No. 5 MP-695-082) is shown in Figure 7 Corresponding scanning electron microscopy (SEM) images of the travoprost- ioaded microparticles comprising 9A PLA are shown in Figure SA. [00031S] The particle size distribution (PSD) of travoprasb-loaded microparticles comprising 5.5E PLA (Lot No, MP-695-097) is shown in Figure 9. Corresponding scanning electron microscopy (SEM) images of the travoprost-loaded micropartides comprising 5.5E PLA are shown in Figure IGA. 10 [000319] The PSD of ail travoprost-loaded micropartcictes was narrow. Moreover, the travoprost-loaded microparticles were shown by the SEM images to have a smooth and spherical morphology. WoBarMes:. produced ..by. W-l [000320] Table 5 provides irtformahon on different microparticles produced with the IDC-l . 15 Table 5 Information on different travoprost partides produced by LDC-1 (including specific micropartide lot number). Microparticle Lot MJ577-187 MJ 577-177 Description 4A Microparticles 9A Microparticles DIO (pm) 18,2 ^6.1 ^50 ^D90 ^m) ^m) U.S ^15.0 M3 ^.0 Tra vo prost Content (%w / w) ks.8 ^42.4 ^24 hr w wfro Release (burst) (%) 111.694 031 Residual DCM (ppm) 9 <1 MJ577-183 5.5E Microparticles ^6.1 13.4 ^25.2 ki.i 16.441 11 [000321] The particle size distribution (PSD) of travoprost-loaded microparticles comprising 4A PLA. (Lot No. MJS77-L87) is Shown in Figure 11. The partide size dlsbtetlon (PSD) of travoprost-loaded microparticles comprising 9A PLA (Lot No. MJ577-177) is shown in Figure 12. The particle size distribution (PSD) of travoprost-loaded microparticles comprising 5.5E HA (Lot No. MJ577-183) Is shown in Figure 13. 20 [000322] The PSD of all travaprost-toaded micropartdcles was narrow. [006323] The AXF-MW can also be applied to produce microparticles with a higher median partide size diameter. Example formulation and AXF-Mini process parameters to yield particles with a larger size (comparable to microparticles in the size range of 20-53 pm that can be obtained by homogenization followed by sieving) are summarized in Table 6 below. The resultant: particles had a particle size distribution of D10 = 30.7 pm; D50 = 37..3 pm- D90 = 454 pm as measured by Malvern Mastersizer 300QE, To achieve this PSD, partides made by AXF-Mini do not require sieving* Table 6 Example formulation and process parameters to yield larger diameter particles (Exemplary microparticle Lot: MP-695-040). Formulation Parameters Continiious Phase (CP) PVA 1% w / w Water QS Dispersed Phase (DP) 7A PLA 34..9% w / v Travoprost load* 50.0% DCM QS AXF-Mini Process Parameters CP flow rate 20 mt / min DP flow rate 0.25 ml / min Membrane size 15 pm Insert: size 9.8 mm Particle Size Distribution DIO 30.7 pm D50 37.3 pm D90 45.1 pm ♦Travoprost load = (amount of travoprost) / [(amount of travoprost) + (amount of PLA)] QS = quantity sufficient. [000324] The travoprost:-loaded microparticles described herein were applied in the manufacturing of ocular 10 implants (see Example 2). EXAMPLE 2: MANUFACTURE OF TRAVOPROST-CONTAINING IMPLANTS [000325] In the following, travoprost-loaded microparticles, in particular the microparticles as described in Example 1, were casted into ocular Implants, For the smaller particle sizes, only one type of travoprost-loaded 15 microparticle was used in each implant formulation. [000326] The freeze-dried microparticles (4A, 7A, 9A and / or 5.¾ depending on the formulation of the implant) were blended and weighed in a syringe in predetermined ratios if more than one particle type was included in the implant, or simply weighed in a syringe if only one particle type was included in the implant. The particles were suspended in water for injection (WH). A multi-arm PEG precursor solution was separately dissolved in sodium phosphate monobasic in a syringe. A trilysine acetate (TLA) buffered solution was transferred into a syringe. All syringes were placed under vacuum. The microparticles and PEG precursor syringes were first mixed and then combined with the TLA buffered solution, which initiated hydrogel formation. The resulting suspension was injected 5 into a small 10 tubing (such as 0,4 mm or 0,5 mm tubing ID), Preparation of Trijysine Acetate (TLA) Solution and Syringe [000327] The amount of Trilysine Acetate (TLA) was calculated based on a one-to-one molar ratio of amines to reactive PEG end groups which form the PEG hydrogel network when mixed in a buffered aqueous solution. The TLA solution was prepared in Sodium Phosphate Dibasic buffer. The pH of the solution was measured and recorded. 10 A pre-defined volume was pipetted Into a separate syringe. The syringe was placed upright Into a beaker and transferred to a vacuum chamber for degassing of the solution. Preparation of Microparticie Syringe [000328] After the micropartictes were weighed into the syringe, WFI was added into the syringe to suspend microparticles. The syringe was placed upright Into a beaker and transferred to a vacuum chamber for degassing of 15 the suspension. Preparation of PEG Syringe [0GO329] A predefined amount of 8ai5k PEG was weighed and transferred to a syringe. Sodium Phosphate Monobasic solution was pipetted into the syringe to dissolve BaiSk PEG-SAZ. The PEG solution was used within 60 minutes after preparation. The syringe was placed upright into a beaker and transferred to a vacuum chamber for 20 degassing of the solution. Casting [000330] For each run a microparticle syringe and PEG syringe were connected by a female to female luer connector. Slow even pressure was used to pass the contents of each syringe back (1 pass) and forth (1 pass) for total 25-50 times to mix the contents of the syringes together. The suspension was pulled into a single syringe and 25 then connected to the TLA syringe. When the content of the syringes was first mixed, a calibrated stopwatch was started to measure the time for the suspension to gel Slow even pressure was used to pass the contents of each syringe back (1 pass) and forth (1 pass) for total 2S-50 times to create the PEG / microparticie / TLA suspension. The suspension was drawn Into one syringe and primed to remove any excess air. [000331] While the suspension was still In liquid form, the syringe is connected to tubing and the suspension 30 was injected into the tubing. Once the tubing was full, it is capped on the bottom end, detached from the syringe and capped at the casting end. The remaining pieces of tubing were filled tn the same manner until the gel sets. [000332] Once al! the tubing per a syringe set had been capped, a small amount of the remaining suspension was placed on a glass slide to monitor gel formation. The suspension was gently tapped with a pipette tip until the suspension begins to strand (Le., remains connected to the pipette tip during a complete tapping cycle). This was repeated for each syringe set (total number of runs or syringe sets is variable depending on batch size). Drying [000333] The tubing was placed on the drying fixture which held the hydrogel strands taut during drying. Each drying fixture could hold up to six strands at a time. The drying fixtures were placed horizontally within, an Incubator set to 32 + / - 1 °C with a nitrogen flow (10 L / min). The hydrogel strands remained in the incubator for 48 to 72 hours for drying. Cutting [000334] The dry strands were removed from the tubing and any strands that were damaged during toe removal process were discarded. The strands were fed into a cutter that cut the strand into approximately 2,0 mm Song implants. During the cutting process, each syringe run was collected: in sterile ciear vials designated with batch number, part number and associated run number and labeled as 'Not Inspected'. If the vials of drug implants were not inspected immediately, they were sealed under a blanket of dry nitrogen in the glovebox and refrigerated. Determi nation of the travonrost content [000335] The travoprost content was determined by testing samples on a Waters Acquity UPlC with PDA. Assay samples were prepared by adding n»30 implants to a 1.0 ml volumetric flask. To that flask, 0.5 ml of acetonitrile was added, and the flask was sonicated for “1 minute to extract travoprost. Then, the sample was diluted to volume with water and the flask was mixed. Samples were then transferred to amber HPLC vials via a micropipette. The assay samples were compared to a standard curve comprised of “500,0 yg / ml serially diluted to ~5.0 pg / ml using a diluent of 70:30 watenacetonltrile. The samples were run on a Waters UPLC with the settings shown in Table 7 Table 7 UPLC settings for travoprast content determination. UPLC 1 Waters Acquity UPLC with PDA Column Waters Acquity UPLC BEH C18 1.7pm 2.1 x 100 mm Column Wash Solvent 50:50 ACNiMeOH Purge Solvent 50:50 IPA:H2O Column Temperature (°C) 40,0 Sample Temperature (°C) 15.0 PDA Detector Wavelength Range fom) 210-400 Resolution (nm) $ 1.2 Mobile Phase A | 0.1% TFA in H2D Mobile Phase B | 0.1% TFA in ACN Flow Rate (ml / min) | 0.600 %MPA I 55.C %MPB ..... ] 45, G .. [000336] The pooled assay of n»30 implants was reported in pg / ml. The average assay per implant was calculated by dividing the reported amount by 30. Assay per implant tot was tested in triplicate. Exemplary implant formifattons contaihina mtcrpartides produced with AXF-Mln> [000337] Implant fcrmnialicns of the present disclosure with one single particle type (smaller particle diameter) are shown in Table 8. Table 8 Nominal (theoretical., not measured) implant formulation (% and pg values given on dry basis). Travoprost (pg) 4A .................... (25.9) 7A 25.9% (25,9) 9A 25.9% (25.9) 5.5E___________________ 25.9% (25.9) 8aI5K PEG SAZ (pg) | 35.7% 35.7% 35.7% 357% (35.7) (35.7) (35.7) ¢35.7) Poly (D,L*Lactide) (pg) 33.7% 33.7% 33.7% 33.7% 100 DL 4 PLA (33.7) (33.7) (33.7) (33.7) 100 DL APLA 33.7% - - - 100 Di 3 PLA 337% * i * 100 DL 5.3E PLA - 33.7% - - - 33.7% [ Sodium Phosphate Monobasic (pg) 1.1% 1.1% 1.1% 1.1% (1-D (1.1) (1.1) d-D Sodium Phosphate Dibasic (pg) 1.3% 1.3% 1.3% 1.3% 1 (1.3) (1.3) (1.3) (1.3) 1 Tfiiysme Acetate (pg) 23% 2.3% 2.3% 2.3% 1 (23) (2.3) (23) (23) I Implant Weight (pg) [ 100 100 100 100 [000338] The microparticle load as well as measured travoprost content for corresponding implants is given in Table 9. 10 Table 9 Mesured travoprost amount and micropartide load. I implant Lot Description Microparticle toad* I Travoprost assay (%w / w) s i MP-695-M1-1 , , . - 59.24 I 26.81 I I (Parhcles from MP 6v5-G7s) j i MP-695-101-2 7A implants (Particles from MS-618-078) 59.56 31.70 MP-695-101-3 9A implants (Particles from MP-695-082) 1 59.82> 31.'75);..... MP-695-104-1 S.5E Implants (Particles from MP-695-097) 59.45 23.50 MP-695-104-3 9A implants (Particles from MP-695-082) t 59.49 27.78 * Microparticle load is defined as the total mass percent of microparticles present in the implant. As the microparticles consist of PLA and travoprost, the microparticle toad is defined as the sum of PLA mass concentration (%w / w) and travoprost mass concentration (%w / w). [000339] Table 10 shows further measured values for representative implant batches. 5 Table 10 Mesured travoprost amount, dimensions, and implant weights. PLA Type 4.5A SA 10.5A 5.5E Lot MP-695-101-1 MP-695-101-2 MP-695-104-3 MP-695-104-1 Travoprost Assay (pg) 26.81 31.70 27.78 23.50 Diameter (mm)1 0.266 0.267 0.266 0.249 Length (mm)1 1.999 1.968 - 1.998 2.015 Implant weight (pg)1 113.8 116.1 126.4 115.9 ’Values are the average of 10 implants. [000340] The implants were inspected by scanning electron microscopy (SEM). 4B shows a 4A implant (with only one type of travoprost particles, wherein said travoprost particles comprise 4A PLA), Fig. 68 shows a 7A implant (with only one type of travoprost particles, wherein said travoprost particles comprise 7A PLA), Fig. 88 10 shows a 9A implant (with only one type of travoprost particles, wherein said travoprost particles comprise 9A PLA), and Fig. 108 shows a 5.5E implant (with only one type of travoprost particles, wherein said travoprost particles comprise 5.SE PLA). Overall, all implants had a uniform appearance. EmuQfelXimB^ [000341] Implant formulations of the present disclosure with one single particle type (smaller particle 15 diameter) are shown in Table 11. Table 11 Nominal (theoretical, not measured) implant formulation (% and pg values given on dry basis). PLA Type 4.5A 10.5A i 5.5E Travoprost (pg) 11.5% ..... ...... .......................... 11,5% 1 ..................................... 11.5% .....(40,1)...................................... 8al5K PEG SAZ (pg) 65.9% (230.3) 65.9% % (230.3) ri 65.9% ...... (230.3) Poly (D,L-Lactide) (pg) 100 DL 4 / 4, SA PLA 100 DL 7 / 8A PLA 100 DL 9 / 10.5A PLA 100 DL 5.5E PLA 14.9% (52.1) O 14.9% (52.1) ) 14.9% 14.9% ......... (52.1) 14.9% Sodium Phosphate Monobasic (pg) 1.6% (5.5) 1.6% i (5.5)..... 1.6% (5.S) ................ Sodium Phosphate Dibasic (pg) 1.9% (6.5) 1.9% • (6.5) 1.9% (6.5) i Trilysine Acetate (pg) 4.2%...... (14.8) 4.2% .............. (14.8) 4.2%.......................... (14.8) Implant Weight (pg) 349.3 349.3 349.3 [000342] Table 12 shows properties of representative implant batches. Table 12 Microparticle load, dimensions, and implant weights. PLA Type 4.5A 10.5A 5.5E Microparticle Lot MJ577-187 MJ577-177 M3S77-183 Implant Lot MJ663-001-1 M3663-001-2 MJ663-001-3 Microparticle Load* (%w / w) 26.6 26.6 26.7 Diameter (mm)1 0.171 0.169 0.171 Length (mm)1 14.33 14.63 14.28 Implant weight .(pg)1...... 376.83 386.68 378.41 ‘Values are the average of 12 implants. * Microparticle toad is defined as the total mass percent of microparticles present in the implant. As the microparticles 5 consist of PLA and travoprost, the micropartide load is defined as the sum of PLA mass concentration (%w / w) and travoprost mass concentration (%w / w). EXAMPLE 3: IN PTT / ?ORELASE MEASUREMENTS [000343] The In vitro release from travoprost-containing implants produced as in particular described under 10 Example 2 was measured in the following. [000344] Z / zWo release measurements were performed under simulated physiological sink conditions using 15 implants in 50 mL of lx PBS, 0.5% polyoxyl 40 hydrogenated castor oil, 0.01% sodium fluoride buffer at pH 7.27.4 at 37 °C or 40°C in a 60 mL polypropylene bottle in a water bath. Sampling is performed at pre-determined time points for subsequent sample analysis on a CIS reversed-phase column using ultra high-performance liquid 15 chromatography with UV detection at 220 nm. ; [000345] In vitro release at 37°C of travoprost from the implants containing microparticles produced with AXF-Mini (formulated according to Table 8; with one single smaller diameter travoprost particle type per implant) is shown in Figure 14. 5 [000346] In vitro release at 37°C of travoprost from the implants containing microparticles produced with LDC-1 (formulated according to Table 11; with one single smaller diameter travoprost particle type per implant) is shown in Figure 15, [000347] In vitro release at 40°C of travoprost from the implants containing microparticles produced with 10 LDC-1 (formulated according to Table 11; with one single smaller diameter travoprost particle type per implant) is shown in Figure 16. [000348] As can be seen from Figures 14 to 16, implants comprising only one single type of smaller diameter travoprost-loaded microparticles provide for release profiles that are near zero-order and / or near-linear fashion. L 15 Th...........larggrsize.....microparticle^ [000349] In vitro release of travoprost is also shown for implants with one or more travoprost particle types per implant having a larger particle size (20-53 pm particle size prepared by homogenization followed by sieving). See Figure 17. See also Figure la and Example 1 (in particular, Table 1) of WO 2021 / 158968. 20 [000350] The approximate duration of near-linear in vitro release provided by the implants of Figures 15 and 16 (produced by LDC-1) and Figure 17 (larger mic-oparticle diameter) is shown in Table 13. Table 13 Duration of near-linear in vitro release as a function of PLA composition and particle size. Release was tested as described above at 37 °C. The particle size was determined by sieving or laser diffraction, respectively. See corresponding release profiles in Figures 15-17, PLA composition Particle size (^ Approximate duration (days) 4A 20-53 (by sieving) 50 47% 4A, 53% 7A 20-53 (by sieving) 60 25% 4A, 40% 7A, 35% 9A 20-53 (by sieving) 90 20% 4A, 20% 7A, 10% 9A, 50% 5.5E 20-53 (by sieving) 120 4A 12 ( DS O by l aser ditiraction) 40 9A 10 (DSO by laser diffraction) 110 5.5E 13 (D50 by laser diffraction) 120 [000351] Surprisingly, an implant containing a single type of smaller size travoprost-toaded microparticles (In particular in case the microparticle comprises 7A PLA, 9A PLA, or 5.5E PLA, respectively), provided for a duration of near-linear in vitro release that is similar to the duration of near-linear in vitro release of an implant that contains a blend Of four different types of larger size travoprost-loaded micropafocles (4A, 7A, 9A, and 5.5E PLA). ,5-¾ for 5 example, Table 13. The fact that only a single PLA microparticle type is required, for example, facilitates the manufacturing as a step of mixing multiple PLA microparticle types Is not required. EXAMPLE 4: INTEGRITY / SOFTNESS OF THE IMPLANT [000352] The implant integrity can be deemed as a qualitative parameter for the softness of the implant with 10 respect to the tissue of the anterior chamber of the eye (in particular, the iridocorneal angle). The implant integrity can be determined based on the criteria shown in Table 14 below. Table 14 Criteria for implant integrity assessment. Scale Description F K M implant. IU > (l.tOMPH aa result nt handling foimiiar h> inttia! dosing) > halter implant, no damag.- as a remit of U-hidling (mrthirioii of degradation ob‘« -i uabip) Soft implant, puusv to damage ♦ fom handling; (significant dvgtadatioiil a Implant not able to be handfod / memmmL not maintain cylindrimd shape whep h.mdk-d. cfiait s tmnphrte Ikpmfmtkin of Fiydiogwl EXAMPLE 5: WATER CONTENT OF THE DRY IMPLANT [000353] A protocol for determining the water content of the intracameral implants of the present disclosure in their dried state Is described in the following. The procedure uses a Karl Fischer coulometrc method. 1.0 PURPOSE To describe the procedure used to determine the water content of Travoprost Intracanalicular inserts (OTX-TP) using a Karl Fischer coulometric method. 2.0 SCOPE This procedure applies to OTX-TP Travoprost intracanalicular inserts requiring water content determination. Note: This test method was validated per TP-1332 / TR-1297 Method Validation for Optimized Water Content Determination of Travoprost Intracanalicular Depots 3.0 REFERENCED DOCUMENTS Document Number Title SOP-10050 Balances SOP-10053 Gloveboxes SOP-10080 Metrohm Karl Fischer Coulometer with 874 Oven Sample Processor using Tiamo software. TP-1332 Method Validation for Optimized Water Content Determination of Travoprost Intracanalicular Depots Protocol TR-1297 Method Validation for Optimized Water Content Determination of Travoprost Intracanalicular Depots Report ■ A ft BEAr2EMTe MATES5T*l 6 umai-t-urr ; Hydranal Water Standard - KF Oven 140-160°C 4.1.1 Reference Standard. The exact water % is specified on the Certificate of Analysis (CoA) for each tot. Reagents 4.2.1 Hydranal Coulomat AG Oven Anolyte Materials 4.3.1 Molecular Sieves, 0.3nm (VWR P / N: EM-MX15B3D-1 or equivalent) 4.3.2 Magnetic stir bar ...... ....... 4.3.3 Crimpers 4.3.4 20mm vials Karl Fischer Vials with septa crimp caps Equipment 4.4.1 Analytical balance 4.4.2 Portable glove box with regulated nitrogen gas supoly 4.4.3 Flow meter, in line between regulated nitrogen supply and glove box. 4.4.4 Karl Fischer Coulometric Titrator equipped with an oven sample processor (autosampler) and Dosino bottle top dispenser. 4.4.5 Karl Fischer Coulometric Titrator with Tiamo software 5.0 EQUIPMENT SET-UP Set up the portable glovebox per SOP-10053 Gloveboxes. Ensure flow meter is sitting vertically and securely. Open the valve on the flow meter fully by rotating dial counter-clockwise until a soft stop is achieved. Open the valve on regulated nitrogen supply and adjust the regulators, if necessary, to achieve a nitrogen flow with at feast ~2-3 psi. This is 'full flow" nitrogen. Purge the glovebox at full flow for at least 30 minutes. Refer to SOP-10080 Kar! Fischer Coulometer with 874 Oven Sample Processor using Tiamo Software for instrument set up and analysis procedure. 5 6.0 BLANK PREPARATION Benchtop Blank preparation - perform in triplicate (n=3) - System Suitability Blanks 6.1.1 Equilibrate an empty vial on benchtop conditions for at least 30 minutes. 6.1.2 Crimp seal the empty vial prior to standard preparation. 10 6.1.3 Place vial in the autosampler. 6.1.4 Analyze blanks for water content according to Section 9.0, Glovebox Blank preparation - perform in triplicate (n=3) - Sample Blanks 6.2.1 Equilibrate an empty vial under full flow nitrogen fcr at least 30 minutes. 6.2.2 Crimp seal the empty vial prior to sample preparation. 15 6.2.3 Place vial in the autosampler. 6.2.4 Analyze blanks for water content according to Section 9.0. 7.0 STANDARD PREPARATION Water standard preparation - perform in triplicate (n=3) 20 7.1.1 Equilibrate an empty vial on benchtop conditions for at least 30 minutes. 7.1.2 Weigh 50,0 ± 5.0 mg of Hydranal water standard with an analytical balance per S0P-1OO5O Balances, directly into a vial that has been equilibrated at benchtop conditions for at least 30 minutes. 7.1.3 Record the exact weight and water content (from CoA) of the standard in the Tiamo software on the 25 appropriate lines. 7.1.4 Crimp seal the vial and place it in the autosampler. 7.1.5 Analyze standards for water content according to Section 9.0. Bracket standard preparation 7.2.2 Equilibrate an empty vial on benchtop conditions for at least 30 minutes. 30 7.2.2 Weigh 50.0 ± 5.0 mg of Hydranal water standard with an analytical balance per SOP-10050, directly into a vial that has been equilibrated at benchtop conditions for at least 30 minutes. 7.2.3 Record the exact weight and water content (from CoA) of the standard in the Tiamo software on the appropriate lines. 7.2.4 Crimp seal the vial and place it in the autosampler. 35^ 7,2.5 Analyze standards for water content according to Section 9.0. 8.0 SAMPLE PREPARATIONS OTX-TP intracanalicular insert sample preparation - Perform in triplicate (n=3) 8.1.1 Equilibrate sample vials and caps under full flow nitrogen for at least 30 minutes. 40 8.1.3 Place cap loosely on vial and remove from glove box. 8.1.3 Obtain the weight of the empty vial and cap for each sample, ensuring that the vial and cap are kept matched together for duration of sample preparation. Record exact weight. 8.1.4 Replace vial and cap in glove box. Allow glove box to re-equilibrate under full flow nitrogen for a minimum of 5 minutes. 45 8.1.5 Just prior to sample preparation, adjust the dial on the flow meter until 4 ± 1 L / min is reached, This is achieved by first rotating the dial clockwise until the flow Is below 4 L / min, then rotating the dial counter clockwise back up to 4 L / min. The flow rate is read at the center of the float, 8.1.6 For each sample, remove cap and place 30 OTX-TP intracanalicular inserts into one vial. 8.1.7 Crimp seal cap onto vial. 50 8.1.8 Remove sealed vial from glove box and obtain weight of vial with inserts. Record exact weight. 8.1.9 Calculate sample weight:Sample Weight (mg)= Weight of vial with Inserts (mg) - Weight of empty vial (mg) 8.1.10 Record the exact weight of the sample in the Tiamo software under the appropriate sample line. ........ 8.1.11 Place sample in the autosampler. 55 8.1.12 Analyze samples for water content according to Section 9.0. 8.1.13 Samples are stable for four hours after preparation under ambient conditions of the instrument. 9.0 ANALYSIS PROCEDURE Procedural References 5 9.1.1 See Figure Id of WO 2021 / 158968 Al for a typical Karl Fischer plot of the blank obtained using this procedure. 9.1.2 See Figure le of WO 2021 / 158968 Al for a typical Karl Fischer plot of the water standard obtained using this procedure. 9.1.3 See Figure If of WO 2021 / 158968 Al for a typical Karl Fischer plot of an OTX-TP sample obtained using this procedure. 10 9.2 Ensure that the Karl Fischer Titrator with oven sample processor system is set to the following parameters: Gas Flow "Wr* ,,,- ,,,.1 y., .,¾. / b mLmrn - Oven Temoerature wc 1 Stir Speed 10 Extraction Time 120 seconds' Start Drift 20 pg / nm Stop Drift 10 pg / min Mwmvn Titration Rate 15 ugrrtn ♦Note: The KF Blank and System Suitability Blank methods use an extraction time of 60 seconds. fiomnonWriaMes 15 9.3.1 Two common variables are required in the Tiarrto software to ensure that the proper blank values are applied to the standard and sample injections. Standards prepared under ambient conditions are corrected for ambient moisture by preparing blanks under ambient conditions. Samples prepared in the glovebox under nitrogen are corrected for glovebox moisture by preparing blanks under glovebox conditions. 20 9.3.1.1 Common Variable #1 ■ System Suitability Blank: This common variable features the average blank value for the three "system suitability blank" injections. This common variable value is used to determine the water content values of the "system suitability standard" and "bracket standard" injections. 9.3.1.2 Common Variable #2 - Sample Blank: This common variable features the average blank value for the three "sample blank" injections. This common variable value is used to determine the water content values of the sample 25 injections. " ..... ;; • ft ..... : Note: For a summary of the common variables used, see the table below: Prepared Conditions Cnnimon M£in% 1 tljSC-ItOttS tflO V'OfTljTlOR W viilMck id AruPiftoH Fa fAr Ptt'inV tfcWtOOSv feRBSWto Subtraction System Surabitty Blanks H-l Anwi (Benchtopj s?Uhu>lJU’.y Dtalln System Suitability Standards. Bechet Standarc SanW Blanks * t-3i Gtovetox “Sample Blank" Samples ; 9.4.1 Load one previously injected blank vial into the autosampler at position 1 and another into the "condition" position. These are for system preparation (equilibration). If previously injected blank vials are not available, use 35 freshly crimped empty vials. Run system preparation at the start of every run using toe "KF System Prep" method in Tiamo. Note: If freshly crimped empty vials 9.4.2 Make one injection of each system suitability blank vial (n=3) using the "System Suitability Blank" method in Tiamo. 9.4.3 Make one injection of each water standard vial (n=3) using the "KF Benchtop Standard" method in Tiamo. 5 9.4.4 Make one injection of each glovebox sample blank vial (n=3) using the "Sample Blank" method in Tiamo. 9.4.5 Make one injection of each glovebox sample vial using the "KF Glovebox Sample" method in Tiamo. 9.4.6 As a system check, make an injection of a bracket standard vial after every 15 samples and at the end of the analysis using the "KF Benchtop Standard" method in Tiamo. 9.5 Example Injection Sequence: Vial # ■: Injection ■ 1 System Prep Vial KF System Prep 2-4 System SuitaWy Blank 1-3 System Suitably Blank .5-7 System Suitability Standard 1-3 KF Sencbtcp Standarc 8-10 Sample Blank 1-3 0-25 : Samples 1-15 KF Giove wk ban pie 26 Bracket Standard KF Benmop Standard 9.6.1 Calculate the percent relative standard deviation (%RSD) for the water % for the 3 consecutive injections of the water standards. The RSD of the water % must be less than or equal to 2.0%. 9.6.2 The Tiamo Software will calculate the percent recovery of the water content for the standard injections against 15 the water content of the CoA. 9.6.2.1 The total average water content percent recovery listed on the third standard must fall in the range of 95.0 -105.0%. 9.6.3 Calculate the recovery of water % for the bracket standard against the total average water content percent for the three system suitability standards as follows: ."OiIf n ..... shvkivds 9.6.3.1 The bracket standard percent recovery must fall in the range of 95.0 - 105.0%. 10.0 SAMPLE CALCULATIONS 25 The Tiamo software will automatically calculate the water % for each sample. 10.1.1 Each sample with a water % value that is less than (<) 1.0%, report as "< 1.0%" 10.1.2 Each sample with a water % value that is greater than or equal to (>) 1.0%, report the value to two decimals. Calculate the mean water % for the 3 samples. 10.2.1 If the water % of all 3 samples are less than 1.0%, report mean water % result as ”< 1.0%". 30 10.2.2 If the water % of any sample is greater than or equal to 1.0%, calculate the mean water % using the values that are > 1.0%. Any values < 1.0% will not be included in the mean water % calculation. 10,2.2.1 Report the mean water % to one decimal. EXAMPLE 6: SYRINGE SUITABLE FOR INJECTING THE INTRACAMERAL IMPLANTS OF THE PRESENT DISCLOSURE [000354] An intracameral implant as described above can be loaded in a 26G or 27G needle attached to a sterile syringe assembly as shown in Figure 18. 5 [000355] Therefore, a wire is inserted in the tip of the needle to retain the implant in the needle during shipping and handling. The syringe assembly containing the implant is sealed within a low vapor-transmission peelable foil-LDPE pouch in a nitrogen environment. The terminal sterilization of the preassembled syringe assembly and final packaged drug product is performed by gamma irradiation at a validated irradiation dose in accordance with ISO 11137-2:2013 Sterilization of Health Care Products - Radiation. The foil pouch provides protection from 10 moisture, oxygen and light, and serves as a sterile barrier for the implant [000356] Container integrity and strength are ensured through two primary tests, bubble emission and seat strength testing. A minimum seal strength of 1.0 Ibf is required for the foil pouch during in-process and stability testing. Additionally, per whole package integrity testing of the foil pouch during shelf life evaluation, it must withstand bubble emission while pressurized at 10 ± 2 inches HzO. Use of the bubble emission test to support the 15 continued capability of container closures to maintain sterility is permitted by FDA Guidance for Industry: Container and Closure System Integrity Testing in Lieu of Sterility Testing as a Component of the Stability Protocol for Sterile Products, February 2008. Drug product packaging and container-closure will be confirmed by stability testing at refrigerated (2 °C - 8 °C) storage conditions. [000357] The component information is provided in Table 15. Table 15 Container Closure System suitable for intracameral implants of the present disclosure. 50 pL Hamilton Syringe Hamilton Company Model 1705TLL Gastight Syringe with PTFE Luer-Lock Hamilton Syringe Lock Clip Proto Labs Inc. Makrolon RX2530-451118 (Blue Tint «1 : ..... .............. ...... : Ultra-Thin Wall 26G or 27G ’ / 2" Needles Nipro Medical Stainless Steel Hypodermic Needle ..... 0.009" OD Nitinol Wire, 1.77" in Length Wytech Industries, Inc. NCT Shape Memory W, (Nittool 55) 0.009" OD Nitinol Wire, 2.00 cm Length Wytech Industries, Inc. i Peelable Foil Pouch (2.5* X 9.581") Hangar Industries, Inc. 48 GA PET / .001 WLDPE / .0007 ALUM F / .0007 LOPE / .002 Peelable Film (MRMPLK235)
Claims
1. A travoprost sustained release biodegradable intracameral implant comprising a biodegradable hydrogel and travoprost particles.,wherein the biodegradable hydrogel comprises a polymer network comprising one or more units of polyalkylene glyco;,wherein the travoprost particles are a mixture of travoprost and a biodegradable polymer, wherein the travoprost particles are dispersed within the biodegradable hydrogel, andwherein the travoprost particles have a median diameter of about 2 pm to about 19 pm as determined by laser diffraction,2. The intracameral implant according to claim 1, wherein the travoprost particles have a median diameter of about 4 pm to about 17 pm or about 5 pm to about 16 pm as determined by laser diffraction,3. The intracameral implant according to claim 1, wherein the travoprost particles have a median diameter of about 6 pm to about 15 pm or about 7 pm to about 14 pm as determined by laser diffraction.4, The intracameral implant according to claim 1, wherein the travoprost particles have a median diameter of about 8 pm to about 13 pm as determined by laser diffraction.
5. The intracameral implant according to claim 1, wherein toe travoprost particles have a median diameter of about 7 pm to about 10 pm or about 8 pm to about 9 pm as determined by laser diffraction.6, The intracameral implant according to claim 1, wherein the travoprost particles have a median diameter of about 8 pm or about 9 pm as determined by laser diffraction,7. The intracameral implant according to claim 1, wherein the travoprost particles have a median diameter of about 9 pm to about 14 pm or about 10 pm to about 13 pm as determined by laser diffraction.
8. The intracameral implant according to ciaim 1, wherein the travoprost particles have a median diameter of about IC pm or about 11 pm as determined by laser diffraction.
9. The intracameral implant according to claim i, wherein the travoprost particles have a median diameter of about 12 pm or about 13 pm as determined by laser diffraction.
10. The intracamerai implant according to claim 1, wherein the particle size distribution of the travoprost partides as determined by laser diffraction is characterized as foltows: D10 of about 3 pm to about 9 pm, D50 of about 7 pm to about 14 pm, and 090 of up to about 50 pm, such as D90 of about 12 to about 26 um.
11. The intracamerai implant according to claim 1, wherein the partide size distribution of the travoprost particles as determined by laser diffraction Is characterized as follows: DIB of about 5 pm to about 9 pm, D50 of about 9 pm to about 14 pm, and D90 Of about 13 pm to about 26 pm.
12. The intracamerai implant according to claim 1, wherein the particle size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: D10 of about 6 pm to about 8 pm, D50 of about 10 pm to about 13 pm, and DSC of about 14 pm to about 25 pm.
13. The intracamerai implant according to claim 1, wherein the particle size distribution of toe travoprost particles as determined by laser diffraction is characterized as follows: D10 of about 3 pm to about 6 pm, D50 of about 7 pm to about 10 pm, and D90 of about 12 pm to about 16 prm14, The intracamerai implant according to claim 1, wherein the particle size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: DIG of about 4 pm to about 5 pm, D50 of about 8 pm to about 9 pm, and D90 of about 13 pm to about 15 pm.
15. The intracamerai implant according to any one of the preceding claims, wherein the travoprost particles comprise about 40 wt-% to about 50 wt-% or about 41 wt-% to about 49 wt-% travoprost based on the total mass of the travoprost particles.
16. The intracamerai implant according to any one of the preceding claims, wherein the travoprost particles comprise about 42 wt-% to about 48 wt-% or about 43 wt-% to about 47 wt-% travoprost based on the total mass of the travoprost particles.
17. The intracamerai implant according to any one of the preceding claims, wherein toe travoprost particles comprise about 42 wt-% to about 44 wt-% or about 45 wt-% to about 47 wt-% or about 46 wt-% to about 48 wt-% travoprost based on foe total mass of the travoprost particles.18, The intracamerai implant according to any one of the preceding claims, wherein the travoprost particles comprise about 40 wt-% to about 47 wt-% or about 41 wt-% to about 46 wt-% travoprost based on the total mass of the travoprost particles,19. The intracamerai implant according to any one of the preceding claims, wherein the travoprost particles comprise about 45 wt-% to about 47 wt-% or about 41 wt-% to about 43 wt-% or about 40 wt-% to about 42 wt-% travoprost based on the total mass of the travoprost particles.
20. The intracameral implant according to any one of the preceding claims, wherein the intracameral implant comprises only one type of travoprost particles.5 21. The intracameral implant according to any one of the preceding claims, wherein the biodegradable polymercomprises or consists of a polyiacfide-co-glycoiide or a polylactide,, optionally wherein the biodegradable polymer comprises ar consists of a polylaaide, such as a poly(DL)i>3ctide.
22. The intracameral implant according to any one of the preceding claims, wherein the biodegradable polymer 10 comprises or consists of a polylactide and wherein the polylactide has an acid end group, optionallywherein the polyiactide is a poly(DL)lactld:e.
23. The intracameral implant according to any one of the preceding claims, wherein the biodegradable polymer comprises or consists of a polyiactide and wherein the polylactide has an ester end group, optionally15 wherein the polyiactide is a poly(DL}lactide.
24. The intracameral implant according to any of the preceding claims, wherein the intracameral implant comprises only one type of travoprost particles, wherein said travoprost particles are a mixture of travoprost and a biodegradable polymer consisting of a polyiactide, wherein said polyiactide:20 -has an Inherent viscosity specification from about 0.50 dl / g to about 1.10 dl / g, such as about 0.60 df / g toabout 1.00 dl / g, as measured at 0.5% w / v in chloroform at 30°C, and optionally has an acid end group., or-has an an inherent viscosity specification from about 0.45 di / g to about 0.85 dl / g, such as about 0.55 dl / g to about 0.75 dl / g, as measured at 0.1% w / v in chloroform at 25’C, and opbonaily has an ester end group.2525, The intracameral implant according to any one of claims 1 to 23, wherein the intracameral implant comprises only one type of travoprost particles, wherein said travoprost particles are a mixture of travoprost and a biodegradable polymer consisting of a polyiactide having an acid end group and an inherent viscosity specification from about 0,25' dl / g to about 0.55 dl / g, such as about 0.35 di / g to about30 0.45 dl / g, as measured at G.5% w / v in chloroform at 30°C>26. The intracameral implant according to claim 25, wherein said travoprost particles comprise about 44 wt-% to about 48 wt-%, such as about 45 wt-% to about 47 wt-% or about 46 wt-%, travoprost based on the total mass of Ihe travoprost particles.3527. The intracameral implant according to claim 25 or 2.6, wherein the particle size distribution of said travoprost particles as determined by laser diffraction is characterized as follows: DiO of about 4 pm to about 6 pm, D50 of about 8 pm to about 10 pm, and DOO of about 13 pm to about 15 pm,optionally wherein the partide size distribution of said travoprost particles as determined by laser diffraction is characterized as follows: DIG of about 5 pm, D50 of about 9 pm, and D9G of about 14 pm..
28. The intracameral implant according to claim 25 or 26, wherein the particle size distribution of said travoprost particles as determined by laser diffraction is characterized as follows; DiO of about 7 pm to about 9 pm, D50 of about 11 pm to about 13 pm, and D90 of about 14 pm to about 16 pm,optionally wherein the particle size distribution of said travoprost particles as determined by laser diffraction is characterized as follows; DIO of about 8 pm, D50 of about 12 pm, and D90 of about 15 pm.
29. The intracameral implant according to any one of claims 1 to 23, wherein the intracsmeral implant comprises only one type of travoprost particles, wherein said travoprost particles are a mixture of travoprost and a biodegradable polymer consisting of a poiyiactide having an acid end group and an inherent viscosity specification from about 0,50 dl / g to about 0,90 dl / g, such as about 0,60 dl / g to about 0.80 d! / g, as measured at 0.5% w / v in chloroform at30°C.
30. The intracamera! Implant, according to claim 29, wherein said travoprost particles comprise about 45 wt-% to about49 wt-%, such as about 46 wt-% to about 48 wt-% or about 47 wt-%, travoprost based on the total mass of the travoprost particles,31. The intracamerai implant according to claim 29 or 30, wherein the particle size distribution of said travoprost particles as determined by laser diffraction is characterized as follows: DiO of about 4 pm to about 6 pm, D50 of about 7 pm to about 9 pm, and D90 of about 12 pm to about 14 pm,optionally wherein the particle size distribution of said travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 5 pm, D50 of about 8 pm, and D90 of about 13 pm.
32. The Intracameral Implant according to any one of claims 1 to 23, wherein the intracameral implant comprises only one type of travoprost particles, wherein said travoprost particles are a mixture of travoprost and a biodegradable polymer consisting of a poiyiactide having an acid end group and an inherent viscosity specification from about 0.70 di / g to about 1.10 di / g, such as about 0,80 dl / g to about 1.00 dl / g, as measured at 0.5% w / v In chloroform at 30°C.
33. The intracameral implant according to claim 32, wherein said travoprost particles comprise about 41 wt-% to about 45 wt-%, such as about 42 wt-% to about 44 wt-% or about 43 wt-%, travoprost based on the total mass of the travoprost particles.
34. The Intracameral implant according to claim 32, wherein said travoprost particles comprise about 40 wt-% to about 44 wt-%, such as about 41 wt-% to about 43 Wt-% or about 42 wt-%, travoprost based on the total mass of the travoprost particles.
35. The Intracameral implant according to any one of claims 32 to 34, wherein the particle size distribution of said travoprost parities as determined by laser diffraction is characterized as follows: DIO of about 3 pm to about 5 pm, 050 of about 7 pm to about 9 pm, and 090 of about 12 pm to about 14 pm,5 optionaliy wherein the particle size distribution of the traycsprost particles as determined by laser diffractionis characterized as follows: D10 of about 4 pm, D50 of about 8 pm, and D90 of about 13 pm.
36. The intracameral implant according to any one of claims 32 to 34, wherein the particle size distribution of said travoprost particles as determined by laser diffraction is characterized as follows; DIO of about 5 pm10 to about 7 pm, OSO of about 9 pm to about 11 pm, and 090 of about 13 pm to about IS pm,optionally wherein the particle size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 6 pm, DSC of about 10 pm, and D90 of about. 14 pm.
37. The intracameral implant according to any one of claims 1 to 23, wherein the intracameral implant15 comprises only one type of travoprost: particles, wherein said travoprost particles are a mixture oftravoprost and a biodegradable polymer consisting of a polylactide having an ester end group and an inherent viscosity specification from about 0.45 dl / g to about 0.85 dt / g, such as about 0.55 dl / g to about 0,75 dl / g, as measured at 0.1% w / v in chloroform at 25*C.20 38. The intracamera! implant according to claim 37, wherein said travoprost particles comprise, about 41 wt-%to about 45 wt-%, such as about 42 wt-% to about 44 wt-% or about 43 wt-%, travoprost based on the total mass of the travoprost particles.
39. The intracameral implant according to claim 37, wherein said travoprast particles comprise about 39 wt~%25 to about 43 wt-%, such as about 40 wt-% to about 42 wt-% or about 41 wt-%, travoprost based on thetotal mass of the travoprost particles.40, The intracameral implant according to any one of claims 37 to 39, wherein the particle size distribution of said travoprost particles as determined by laser diffraction is characterized as follows: DiO of about 4 pm 30 to about 6 pm, D50 of about 8 pm to about 10 pm, and D90 of about 14 pm to about 16 pm,opttonaily wherein the particle size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 5 pm, D50 of about 9 pm, and D90 of about 15 pm.
41. The intracameral implant according to any one of claims 37 to 39, wherein the particle size distribution of35 said travoprost particles as determined by laser diffraction is characterized as follows: D10 of about 5 pmto about 7 pm, D50 of about 12 pm to about 14 pm, and D90 of about 24 pm to about 26 pm, optionally wherein the particle size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: DiO of about 6 pm, D50 of about 13 pm, and D90 of about 25 pm.
42. The intracameral implant according to any one of the preceding claims, wherein toe travoprost particles are obtained by or are obtainable by a process comprising a membrane emulsification step.
43. The intracameral implant according to any one of the preceding claims, wherein the implant has a length of about 1.50 mm to about 2.50 mm and a diameter of not more than 0.30 mm in its dried state.
44. The intracameral implant according to any one of the preceding claims, wherein the implant has a length of about 1.60 mm to about 2.40 mm or about 1.70 mm to about 2.30 mm in its dried state.
45. The intracameral implant according to any one of the preceding claims, Wherein toe implant has a length of about 1.80 mm to about 2.20 mm or about 1.90 mm to about 2.10 mm in its dried state.
46. The intracameral implant according to any one of the preceding claims, wherein toe implant has a length of about 1.95 mm to about 2.05 mm, such as about 2.00 mm, in its dried state.
47. The intracameral implant according to any one of the preceding claims, wherein the implant has a diameter of about 0.20 mm to about 0.30 mm or about 0,23 mm to about 0.29 mm in its dried state.
48. The intracameral implant according to any one of the preceding claims, wherein toe implant has a diameter of about 0.24 mm to about 0.28 mm or about 0.25 mm to about 0,27 mm in its dried state.
49. The intracameral implant according to any one of the preceding claims, wherein toe implant has a diameter of about 0.25 mm, about 0.26 mm, or about 0.27 mm in its dried state.
50. The Intracameral implant according to any one of the preceding claims, wherein the implant has a length of about 1,90 mm to about 2,10 mm and a diameter of about 0.24 mm to about 0.28 mm in its dried state.
51. The intracameral implant according to any one of the preceding claims, wherein the content of travoprost with respect to the total weight of the intracameral implant in its dried state is about 10 wt-% to about 40 wt-% or afloat 15 wt-% to about 35 wt-%.52, The intracameral implant according to any one of the preceding claims, wherein the content of travoprost with respect to the total weight of the intracameral implant in its dried state is about 20 wt-% to about 30 wt-% or about 25 wt-% to about 30 wt-%.
53. The intracameral implant according to any one of the preceding claims, wherein toe content of travoprost' with respect to the total weight of the intracameral implant In its dried state is about 22 wt-% to about 30 wt-% or about 24 wt-% to about 28 wt-% of travoprost.
54. The intracameral implant according to any one of the preceding claims, wherein the content of travoprost with respect to the total weight of the intracamera! implant in its dried state is about 25 wt-% to about 27 wt-% or about 26 wt-%.
55. The intracameral implant according to any one of the preceding claims, wherein the implant comprises a dose of about 10 pg to about 40 pg or about 15 pg to about 35 pg of travoprost56. The intracameral implant according to any one of the preceding claims, wherein the implant comprises a dose of about 20 pg to about 30 pg or about 25 pg to about 30 pg of travoprost.
57. The intracameral implant according to any one of the preceding claims, wherein the implant comprises a dose of about 22 pg to about 30 pg or about 24 pg to about 28 pg of travoprost.
58. The intracameral implant according to any one of the preceding claims, wherein the implant comprises a dose of about 25 pg to about 27 pg or about 26 pg of travoprost.
59. The intracameral implant according to any one of the preceding claims, wherein the implant is in the form of a fiber.
60. The intracameral implant according to any one of the preceding claims, wherein the implant has a total weight of about 50 pg to about 150 pg, or of about 75 pg to about 125 pg in its dried state,61. The intracameral implant according to any one of the preceding claims, wherein the implant has a total weight of about 80 pg to about 120 pg or of about 90 pg to about 110 pg in its dried state,62, The intracameral implant according to any one of the preceding claims, wherein the implant has a total weight of about 95 pg to about 105 pg in its dried state.
63. The intracameral implant according to any one of the preceding claims, wherein the implant has a total weight of about 100 pg in Its dried state.64, The intracameral implant according to any one of the preceding claims, wherein the content of the biodegradable polymer with respect to the total weight of the intracameral implant In Its dried state is about 29 wt-% to about 39 wt-% or about 31 wt-% to about 37 wt-%,65. The intracameral implant according to any one of the preceding claims, wherein the content of the biodegradable polymer with respect to the total weight of the intracameral implant in its dried state is about 32 wt-% to about 36 wt-% or about 33 wt-% to about 38 wt-% or about 34 wt-%.
66. The intracameral implant according to arty one of the preceding claims, wherein the total mass of the biodegradable polymer in the implant in its dried state is about 29 pg to about 39 pg or about 31 pg to about 37 pg,67. The intracameral implant according to any one of the preceding claims, wherein the total mass of the biodegradable polymer in the implant in its dried state is about 32 pg to about 36 pg or about 33 pg to about 35 pg or about 34 pg>■68. The intracameral implant according to any one of claims 1 to 42, wherein the implant has a length of about 13.00 mm to about 16.00 mm and a diameter of not more than 0.20 mm in its dried state.69, The irtracamerai implant according to claim 68, wherein the implant has a length of about 14.00 mm to about 15.00 mm in its dried state.
70. The intracameral implant according to claim 68 or 69, wherein the implant has a diameter of about 0.10 mm to about 0.20 mm or about 0.15 mm to about 0.20 mm in its dried state.
71. The intracameral implant according to ciaim 70, wherein the implant has a diameter of about 0.16 mm to about 0..18 mm or about 0.17 mm tn its dried state.
72. The intracameral implant according to any one of claims 1 to 42 and 68 to 71, wherein the content of travoprost with respect to the total weight of the intracameral implant in its dried state is about 2 wt-% to about 22 wt-% or about 4 wt-% to about 20 wt-%.
73. The intracameral implant according to claim 72, wherein the content of travoprost with respect to the total weight of the intracameral implant in its dried: state is about 7 wt-% to about 17 wt-% or about 10 wt-% to about 14 wt-%.74, The intracameral implant according to claim 73, wherein the content of travoprost. with respect to ths total weight of the intracameral implant in its dried state is about 11 wt-% to about 13 wt-% or about 12 wt-% of travoprost.
75. The intracameral implant according to any one of claims 1 to 42 and 68 to 74, wherein the implant comprises a dose of about 30 pg to about 50 pg or about 35 pg to about 45 pg of travoprost76. The intracameral implant according to claim 75, wherein the implant comprises a dose of about 36 pg to about 44 pg or about 37 pg to about 43 pg of travoprost77. The intracameral implant according to claim 76, wherein the impiant comprises a dose of about 38 pg to about 42 pg or about 39 pg to about 41 pg of travoprost.
78. The intracameral implant according to claim 77, wherein the implant comprises a dose of about 40 pg of travoprost,79. The intracameral implant according to any one of claims 1 to 42 and 68 tn 78, wherein the implant is In toe form of a fiber.
80. The intracameral implant according to any one of claims 1 to 42 and 68 to 79, wherein the implant has a total weight of about 300 pg to about 400 pg, or of about 320 pg to about 380 pg in Its dried state.
81. The intracameral implant according to claim 80, wherein the implant has a total weight of about 330 pg to about 370 pg or of about 340 pg to about 360 pg in Its dried state.
82. The intracameral implant according to claim 81, wherein the implant has a total weight of about 345 pg to about 355 pg in its dried state.
83. The intracameral implant according to claim 82, wherein the implant has a total weight of about 350 pg in its dried state.
84. The intracameral implant according to any one of claims 1 to 42 and 68 to 83, wherein the content of the biodegradable pdymer with respect to the total weight of the intracameral implant in its dried state is about IQ wt-% to about 20 wt-% or about 12 wt-% to about 18 wt-%>85. The intracameral implant according to claim 84, wherein the content of the biodegradable polymer with respect to the total weight of the intracameral implant in Sts dried state is about 13 wt-% to about 17 wt-% or about 14 wt-% to about 16 wt-% or about 15 wt-%.
86. The intracameral implant according to any one of claims 1 to 42 and 68 to 85, wherein the total mass of the biodegradabie polymer in the Implant in its dried state is about 47 pg to about 57 pg or about 49 pg to about 55 pg.
87. The intracameral implant according to ciaim 86, wherein the total mass of the biodegradable polymer inthe implant in its dried state is about 50 pg to about 54 pg or about 51 pg to about 53 pg or about 52 pg.
88. The intracameral implant according to any one of the preceding claims, wherein the polymer network comprises one or more units of polyethylene glycol.
89. The intracamera! impfant according to arty one of the preceding claims, wherein the polymer network.comprises one or more units of polyethylene glycol being cross-linked inciuding a group represented by the following formula:wherein m is 1, 2, 3, and / or 6, such as wherein m is 6.
90. The intracamerai implant according to any one of the preceding claims, wherein the polymer network comprises one or more units of a multi-arm polyethylene glycol having from 2. to 10 arms or from 4 to 8 arms, 1091. The intracamerai implant according to any one of the preceding claims, wherein the polymer network comprises one or mare units of a multi-arm polyethylene glycol having 4 arms or 8 arms, such as 8 arms,92, The intracamerai implant according to any one of the preceding claims, wherein the multi-arm polyethylene 15 glyco! has an average molecular weight from about 10,000 Da to about 20,000 Da or from about 12,500Da to about 17,500 Da, such as about JS.OOO Da.93.. The intracamerai implant according to any one of claims 1 to 88, wherein the polymer is formed by reacting an electrophilic group-containing multi-arm polyethylene glycol precursor with a nucleophilic20 group-corrtainmg cross-iinkJng agent.
94. The intracamerai implant according to claim 93, wherein the nucleophilic group is an amine.
95. The intracamerai implant according to claim 94, wherein the nucleophilic group-containing cross-linking 25 agent has a molecular weight below 1,000 Da and comprises two or more primary aliphatic amine groups.
98. The intracamerai implant: according to any one of claims 93 to 95, wherein the nucleophilic group-containing cross-linking agent is a diSysine, trilysine, tetralysine, ethytenediamlne, 1,3-diaminopropane, 1,3-diaminopropane, diethySeneWamine, or frimethylhexamethytenediamine.3097. The intracamerai implant according to claim 96, wherein the nucleophilfc group-containing cross-linking agent is a trilysine, such as a salt of trilysine, such as trilysine acetate.
98. The intracamerai implant according to any one of claims 93 to 97, wherein the electrophilic group is succinimidyi glutarate (SG), succiriimidyl succinate (SS), succinimidy! carbonate (SC), sucdnimidyl adipate (SAP), and / or succtnimidyi azelate (SAZ).5 99. The intracamerai implant according to claim 98, wherein the electrophilic group is succinimidyl azelate(SAZ).100.The intracamerai implant according to any one of claims 93 to 99, wherein the polyethylene glycol precursor has from 2 to 10 arms or from 4 to 8 arms.10101.The intracamerai implant according to any one of claims 93 to 100, wherein the polyethylene glycol precursor has 4 arms or 8 arms, such as 8 arms.102.The intracamerai Implant according to any one of claims 93 to 101, wherein the multi-arm polyethylene 15 glycol tn the multi-arm polyethylene glycol precursor has an average molecular weight from about 10,000Da to about 20,000 Da or from about 12.,500 Da to about 17,500 Da, such as about 15,000 Da,103.The intracamerai implant according to any one of claims 93 to 102, wherein the electrophilic group-containing mult-arm polyethylene glycol precursor is 8-arm-15K-PEG-SAZ.20104.The intracamerai implant according to any one of claims 93 to 103, wherein the weight ratio of tire electrophilic graup-containing multi-arm polyethylene glycol precursor to the nucleophilic group-containing cross-linking agent Is from about 14:1 to about 18:1, or from about 15:1 to about 17:1, or about 16:1.25 lOS.The intracamerai implant according to any one of the preceding claims, wherein the content of the biodegradable hydrogel with respect to the total weight of the intracamerai implant in its dried state Is about 30 wt-% to about 50 wt-% or about 34 wt-% to about 42 wt-%.106.The intracamerai implant according to any one of the preceding claims, wherein the content of the30 biodegradable hydrogel with respect to the total weight of the intracamerai implant in. its dried state Isabout 35 wt-% to about 45 wt-% or about 36 wt-% to about 40 wt-%.197.The intracamerai implant according to any one of the preceding claims, wherein the content of the biodegradable hydrogel with respect to the total weight of the intracamerai implant tn its dried state Is 35 about 37 wt-% to about 39 wt-% or about 38 wt-%.lOS.The intracamerai implant according to any one of the preceding claims, wherein the total mass of the biodegradable hydrogel in the intracamerai implant in its dried state is about 30 pg to about 50 pg or about 34 pg to about 42 pg.lOS.The intracameral implant according to arty one of the preceding claims, wherein the total mass of the biodegradable hydrogel in the intracameral: implant in Its dried state is about 35 pg to about 45 pg or about 36 pg to about 40 pg,llO.The intracameral implant according to any one of the preceding claims, wherein the total mass of the biodegradable hydrogel in the intracameral implant in its dried state is about 37 pg to about 39 pg or about 38 pg.111 .The intracameral implant according to any one of claims 1 to 104, wherein the content of the biodegradable hydragel with respect to the total weight of the intracameral implant in its dried state is about 60 wt-% to about SO wt-% or about 65 wt-% to about 75 wt-%.112,The intracameral implant according to claim 111, wherein the content of the biodegradable hydrogel with respect to the totai weight of the intracameral implant in its dried state is about 67 wt-% to about 73 wt-% or about 68 wt-% to about 72 wt-%.113.The intracameral implant according to claim 112, wherein the content of the biodegradable hydrogel with respect to the total weight of the intracameral implant in its dried state is about 69 wt-% to about 71 wt-% or about 70 wt-%.114.The intracamerai implant according to any one of claims 1 to 104 and 111 to 113, wherein the total mass of the biodegradable hydrogel in the intracameral implant in its dried state is about 230 pg to about 260 pg or about 235 pg to about 255 pg.115.The intracameral implant according to claim 114, wherein the total mass of the biodegradable hydrogel in the intracamerai Implant in its dried state is about 240 pg to about 250 pg or about 242 pg to about: 248 pg.116.The intracameral implant according to claim 115, wherein the total mass of the biodegradable hydrogel in the intracameral implant in its dried state is about 244 pg to about 246 pg or about 245 pg.117,The intracameral implant according to any one of the preceding claims, wherein the Implant shows a travoprost in vitro release of less than about: 60% or less than about: 25% or less than about: 20% based on the total weight of travoprost in the intracameral implant after incubating the intracameral implant for 1 day under simulated physiological sink conditions io 50 ml of lx PBS, 0.5% castor oil, 0.01% sodium fluoride buffer at pH 7.2-7.4 at 37 °C.IlS.The intracameral implant according to any one of the preceding claims, wherein the impiant shows a travoprost in vitro release of about 10% to about 25% or about 10% to about 20% based on the totalweight of travoprost in the intracameral implant after incubating the intracamera! implant for 1 day under simulated physiological sink conditions in 50 ml of lx PBS, 0.5% castor oil, 0.01% sodium fluoride buffer at pH 7,2-7.4 at 37 °C,119.The intracameral implant according to any one of the preceding claims, wherein the implant shows a travoprast in vitro release of less titan about 50% or less than about 40% or less than about 30% based on the total weight of travoprast in the intracameral implant after incubating the intracameral implant far 20 days under simulated physiological sink conditions in 50 mL of lx PBS, 0<5% castor oil, 0.01% sodium fluoride buffer at pH 7.2-7,4 at 37 °C.12O.The intracameral implant according to any one of the preceding claims, wherein the implant shows a travoprast in vitro release of less than about 80% or less than about 70% or less than about 50% based on the total weight of travoprost in the intracameral implant after incubating the intracameral implant for 40 days under simulated physiological Sink conditions in 50 ml of lx PBS, 0.5% castor oil, 0,01% sodium fluoride buffer at pH 7.2-7.4 at 37 °C.121 .The intracameral implant according to any one of the preceding claims, wherein the implant shows a travoprast in vitro release of less than about 80% or less than about 70% based on the total weight of travoprost tn the intracameral implant after incubating the intracameral implant for 60 days under simulated physiological sink conditions in 50 mb of lx PBS, 0,5% castor oil, 0,01% sodium fluoride buffer at pH 7.2-7.4 at 37 °C,122.The intracameral implant according to any one of the preceding claims, wherein the implant shews a travoprost in vitro release of less than about 100% or less than about 90% based on the total weight of travoprost in the intracameral implant after incubating the intracamera! implant for 80 days under simulated physiological sink conditions in 50 mt of lx PBS, 0,5% castor oil, 0,01% sodium fluoride buffer at pH 7.2-7.4 at 37 &C.123.The intracameral implant according to any one of the preceding claims, wherein the implant shows a travoprost in vitro release of less than about 100% or less than about 90% based on the totai weight of travoprost in the intracameral implant after incubating the Intracamera! implant for 100 days under simulated physiological sink conditions in 50 mL Of lx PBS, 0.5% castor oil, 0.01% sodium fluoride buffer at pH 7.2-7.4 at 37 °C,124.The intracameral implant according to any one of the preceding claims, wherein the implant shows an essentially zero-order travoprost in vitro release profile when incubating the intracamera! implant under simulated physiological sink conditions in 50 ml of lx PBS, 0.5% castor oil, 0.01% sodium fluoride buffer at pH 7.2-7.4 at 37 °C, optionally when incubating the intracameral implant far about 0.5 months or longer,or about 1 month or longer, or about 1.5 months or longer, or about 2 months or longer, or about 2.5 months or longer, or about 3 months or longer, or about 3.5 months or longer, or about 4 months.125.The intracamerai implant according to any one of the preceding claims, wherein the implant shows an essentially linear travoprost in vitro release profile when incubating the intracamerai implant under simulated physiological sink conditions in 50 ml of lx PBS, 0.5% castor oil, 0.01% sodium fluoride buffer at pH 7.2-7.4 at 37 °C, optionally when incubating the intracameral implant for about 0.5 months or longer, or about 1 month or longer, or about 1.5 months or longer, or about 2 months or longer, or about 2.5 months or longer, or about 3 months or longer, or about 3.5 months or longer, or about 4 months.126.A kit comprising an intracameral implant according to any one of the preceding claims and an injection device for intracameral Injection of the intracameral implant, optionally wherein the injection device is a syringe and / or wherein the Injection device is loaded with the in&acamerai implant.127.A syringe for intracameral injection, wherein the syringe is loaded with an intracameral implant according to any one of claims 1 to 125.128.Travoprost particles, wherein the travoprost particles are a mixture of travoprost and a biodegradable polymer and wherein the travoprost particles have a median diameter of about 2 pm to about 19 pm as determined by laser diffraction.129.The travoprost particles according to claim 128, wherein the travoprost particles have a median diameter of about 4 pm to about 17 pm or about 5 pm to about 16 pm as determined by laser diffraction.130>The travoprost particles according to claim 128, wherein the travoprost particles have a median diameter of about 6 pm to about IS pm or about 7 pm to about 14 pm as determined by laser diffraction,131.The travoprost particles according to claim 128, wherein the travoprost particles have a median diameter of about S pm to about 13 pm as determined by laser diffraction,132.The travoprost particles according to claim 128, wherein the travoprost particles have a median diameter of about 7 pm to about 10 pm or about 8 pm to about 9 pm as determined by laser diffraction.133,The travoprost particles according to claim 128, wherein the travoprost partides have a median diameter of about 8 pm or about 9 pm as determined by laser diffraction.IM.The travoprost particles according to claim 128, wherein the travoprost particles have a median diameter of about 9 pm to about 14 pm or about 10 pm to about 13 pm as determined by laser diffraction.135,The travoprost particles according to claim 128, wherein the travoprost particles have a median diameter of about 1C pm or about 11 pm as determined by laser diffraction..136.The travoprost particles according, to claim 128, wherein the travoprost partides have a median diameter of about 12 pm or about 13 pm as determined by laser diffraction.137 .The travoprost partides according to claim 128, wherein the partide size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: 010 of about 3 pm to about 9 pm, D50 of about 7 pm to about 14 pm, and D90 of up to about 50 pm, such as D90 of about 12 to about 26 pm.1.38.The travoprost particles according to claim 128, wherein the particle size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: DiO of about 5 pm to about 9 pm, D50 of about 9 pm to about 14 pm, and D90 of about 13 pm to about 26 pm.139.The travoprost particles according to claim 128, wherein, the particle size distribution of the travoprost particles as determined by laser diffraction, is characterized as foiiows: DIO of about 6 pm to about 8 pm, D58 of about. 10 pm to about 13 pm, and D90 of about 14 pm to about 25 pm.140.The travoprost partides according to claim 128, wherein the partfete size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 3 pm to about 6 pm, OSO of ateut 7 pm to about 10 pm, and D9C of about 12 pm to about 16 pm.141.The travoprost particles according to claim 128, wherein the partide size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: D10 of about 4 pm to about 5 pm, D50 of about 8 pm to about 9 pm, and D90 of about 13 pm to about IS pm.142,The travoprost particles according to any one of claims 128 to 141, wherein the travoprost particles comprise about 40 wt-% to about 50 wt-% or about 41 wt-% to about 49 wt-% travoprost based on the total mass of the travoprost partides.143.The travoprost particles according to any one of claims 128 to 142, wherein the travoprost particles comprise about 42 wt-% to about 48 wt-% or about 43 wt-% to about 47 wt-% travoprost based on the tote! mass of the travoprost particles,144.The travoprost particles according to any one of claims 128 to 143, wherein the travoprost particles comprise about 42. wt-% to about 44 wt-% or about 45 wt-% to about 47 wt-% or about 46 wt-% to about 48 wt-% travoprost based on the total mass of the travoprost particles.145,The travoprost particles according to any one cF claims 128 to 144, wherein the travoprost partides comprise about 40 wt-% to about 47 wt-% or about 41 wt-% to about 46 wt-% travoprost based on the total mass of the travoprost partides,5 146.The travoprost particles according to any one of claims 128 to 145, wherein the travoprost partidescomprise about 45 wt-% to about 47 wt-% or about 41 wt-% to about 43 wt-% or about 40 wt-% to about 42 wt-% travoprost based on the total mass of the travoprost particles.147.The travoprost particles according to any one of claims 128 to 146, wherein the biodegradable polymer10 comprises or consists of a poiyiactide co giycolide or a poiyiactide.14S,The travoprost particles according to any one of claims 128 to 147, wherein toe biodegradable polymer comprises or consists of a poiyiactide, such as a poiy(DL)iactfde,15 149.The travoprost partides according to any one cf claims 12S to 148, wherein the biodegradable polymercomprises or consists of a polylactide arid wherein the poiyiactide has an acid end group, optionally wherein the polylactide is a poiy(DL)lactide.iSO.The travoprost particles according to any one of claims 128 to 149, wherein the biodegradable polymer 20 comprises or consists of a polylactide and wherein the poiyiactide has an ester end group, optionallywherein the polylactide is a po!y(DL}factide.151 .The travoprost partides according to any one of ciaims 128 to 150, wherein said travoprost particles are a mixture of travoprost: and a biodegradabie polymer consisting of a poiyiactide, wherein said poiyiactide:25 -has an inherent viscosity specification from about 0,50 dl / g to about 1.10 dl / g, such as about 0.60 dl / g toabout 1-00 dl / g, as measured at 0,5% w / v in chloroform at 3G°C, arid optionally has an acid end group, nr-has an an inherent viscosity specification from about 0.45 dl / g to about 0.85 dl / g, such as about 0.55 dl / g to about 0.75 di / g, as measured at 0.1% w / v in chloroform at 25°C, and optionally has an ester end group. 30152,The travoprost particles according to any one of claims 128 to 150, wherein said travoprost particles are a mixture of travoprost and a biodegradable polymer consisting of a poiyiactide having an acid end group and an inherent viscosity specification from about 0,25 dl / g to about 0.55 dl / g, such as about 0.35 dl / g to about 0,45 dl / g, as measured at 0,5% w / v in chloroform at 30®C35'153.The travoprost particles according to claim 152, wherein said travoprost particles comprise about 44 wt-% to about 48 wt-%, such as about 45 wt-% to about 47 wt-% or about 46 wt-%, travoprost based on the total mass of the travoprost particles.154.The travoprost particles according to claim 152 or 153, wherein the particle size distribution of said travoprost particles as determined by laser diffraction is characterized as follows: DIG of about 4 pm to about 6 pin, 050 of about 8 pm to about 10 pm, anti 090 of about 13 pm to about 15 pm, optionally wherein the particle size distribution of said tra voprost particles as determined by laser diffraction 5 is characterized as follows: DIO of about 5 ym, 050 of about 9 gm, and D90 of about 14 pm.155.The travoprost particles according to claim 152 or 153, wherein the particle. size distribution of said travoprost particles as determined by laser diffraction is characterized as follows; DIG of about 7 pm to about 9 pm, D50 of about 11 pm to about 13 pm, and D90 of about 14 pm to about 16 pm,10 optionally wherein the particle size distribution of said travoprost particles as determined by laser diffractionIs characterized as follows: DIO of about 8 pm, DSO of about 12 pm, and D90 of about 15 pm.156.The travoprost particles according to any one of claims '128 to .150, wherein said travoprost particles are a mixture of travoprost and a biodegradable polymer consisting of a polylactide having an add end group15 and an inherent viscosity specification from about 0.50 dl / g to about 0.90 dl / g, such as about 0.60 dl / g toabout 0.80 dl / g, as measured at 0.5% w / v in chloroform at 30°C.157.The travoprost particles according to claim 156, wherein said travoprost particles comprise about 45 wt-% to about 49 wt-%, such as about 46 wt-% to about 48 wt-% or about 47 wt-%, travoprost based on the 20 total mass of the travoprost particles.158,The- travoprost: particles according to claim 156 or 157, wherein the particle size distribution of said travoprost particles as determined by laser diffraction is characterized as follows: DIG of about 4 pm to about 6 pm, DSO of about 7 pm to about 9 pm, and DSO of about 12 pm to about 14 pm,optionally wherein the particle size distribution of said travoprost particles as determined by laser diffraction is characterized as follows; DIO of about 5 pm, D50 of about 8 pm, and D90 of about 13 pm.159.The travoprost particles according to any one of claims 128 to 150, wherein said travoprost particles are a mixture of travoprost: and a biodegradable polymer consisting of a polylactide having an acid end group30 and an inherent viscosity specification from about 0.70 dl / g to about 1.10 dl / g, such as about 0.80 dl / g toabout 1.00 dl / g, as measured at 0.5% w / v in chloroform at 30sC160,The travoprost particles according to claim 159, wherein said travoprost particles comprise about 41 wt-% to about 45 wt-%, such as about 42 wt-% to about 44 wt-% or about: 43 wt-%, travoprost based on the 35 total mass of the travoprost particles.ISl.The travoprost particles according to claim 159, wherein said travoprost particles comprise about 40 wt-% to about 44 wt-%, such as about 41 wt-% to about 43 wt-% or about 42 wt-%, travoprost based on the tote! mass of the travoprost particles,162,The travoprost particles according to any one of claims 159 to 161, wherein the particle size distribution of said travoprost particles as determined by laser diffraction is characterized as fellows: DIG of about 3 pm to about 5 pm, OSO of about 7 pm to about 9 gm, and D9G of about 12 pm to about 14 pm,optionally wherein the particle size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: DiO of about 4 pm, D50 of about 8 pm, and D90 of about 13 pm.163.7116 fravoprost parades according to any one of claims 159 to 161, wherein the particle size distribution of said travoprost particles as determined by laser diffraction is characterized as fallows: DIO of about S pm to about 7 pm, 050 of about 9 pm to about 11 gm, and D90 of about 13 pm to about 15 pm,optionally wherein toe particle size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: DiO of about 6 pm, D50 of about 10 pm, and D9Q of about 14 pm.164.The travoprost partides according to any one of claims 128 to 150, wherein said travoprost particles are a mixture of travoprost and a biodegradable polymer consisting of a polylactide having an ester end group and an inherent viscosity specification from about 0.45 dl / g to about 0.85 d! / g, such as about 0.55 dl / g to about 0.75 di / g, as measured at 0.1% w / v in chloroform at 25°C.165.1316 travoprost particles according to claim 164, wherein said travoprost partides comprise about 41 wt-% to about 45 wt-%, such as about 42 wt-% to about 44 wt-% or about 43 wt-%, travoprost based on the total mass of the travoprost particles.166.The travoprost particles according to claim 164, wherein said travoprost particles comprise about 39 wt-% to about 43 wt-%, such as about 40 wt-% to about 42 wt-% or about 41 wt-%, travoprost based on the total mass of toe travoprost particles.167.The travoprost particles according to any one of claims 164 to 165, wherein the particle size distribution of said travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 4 pm to about 8 pm, D50 of about 8 pm to about 10 pm, and D90 of about 14 ym to about 16 pm, optionally wherein toe particle size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 5 pm, D50 of about 9 pm, and D90 of about 15 um.168.The travoprost particles according to any one of claims 164 to 166, wherein toe particle size distribution of said travoprost: particles as determined by laser diffraction is characterized as follows; DIO of about S pm to about 7 pm, D50 of about 12 pm to about 14 pm, and D90 of about 24 pm to about 26 pm,optionally wherein the partide size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: D10 of about 6 pm, 050 of about 13 pm, and D90 of about 25 pm.169.The travoprost particles according to any one of claims 128 to 168, wherein the travoprost particles are obtained by or are obtainable by a process comprising a membrane emulsification step.170 .The travoprost particles according ta claim any one of claims 128 to 169, wherein the travoprost particles are obtained by or are obtainable by a process comprising:-providing or preparing a first solution comprising travoprost and the biodegradable polymer,-providing or preparing a second solution, wherein the second solution is an aqueous solution, and-passing the first solution through a membrane with pores into the second solution to provide the travoprost particles, optionally wherein the membrane pore size is from about 2.5 pm to about 7.5 pm, such as about 5 pm.171 .The travoprost particles according to any one of claims 128 to 169, wherein the travoprost partides are obtained by or are obtainable by a process comprising:■providing or preparing a first solution comprising travoprost and the biodegradable polymer,-providing or preparing a second solution, wherein the second solution is an aqueous solution,-passing the first solution through a membrane with pores into the second solution to provide the travoprost particles, optionally wherein the membrane pore size is from about 2.5 pm to about 7.5 pm, such as about 5 pm, and-hardening the travoprost particles.172,The travoprost particles according to any one of claims 128 to 169, wherein the travoprost particles are obtained by or are obtainable by s process comprising:-providing or preparing a first solution comprising travoprost and the biodegradable polymer,-providing or preparing a second solution, wherein the second solution is an aqueous solution,-passing the first solution through a membrane with pores into the second solution to provide the travoprost particles, optionally wherein the membrane pore size is from about 2.5 pm to about 7.5 pm, such as about 5 pm,-hardening the travoprost particles, and-purifying the hardened travoprost particles.173,The travoprost: particles according to any one of claims 128 to 169, wherein the travoprost particles are obtained by or are obtainable by a process comprising:-providing or preparing a first solution comprising travoprost and the biodegradable polymer,-providing or preparing a second solution, wherein the second solution is an aqueous solution,■■passing the first solution through a membrane with pores into the second solution to provide the travoprost particles, optionally wherein the membrane pore size is from about 2.5 pm to about 7.5 pm, such as about 5 pm,-hardening the travoprost particles,5 -purifying the travoprost particles, and-drying the travoprost particles.174.The travoprost particles according to any one of claims 170 to 173, wherein the first solution is an organic solution of travoprost and the biodegradable polymer, 10 optionally wherein the organic solvent is dichloromethane and / oroptionally wherein the concentration of the biodegradable polymer in the first solution is from about 30 % w / v to about 40% w / v, such as about 35% w / v, and the concentration of travoprost in the first solution is from about 20% to about 35% w / v, such as about 25% to about 30% w / v, or wherein the concentration of the biodegradable polymer in the first solution is from about 20 % w / v to about 45% w / v and the15 concentration of travoprost in the first solution Is from about 40 % to about 65% w / v, such as about 50%w / v.175.The travoprost particles according to any one of claims 170 to 174, wherein the second solution is an aqueous solution of polyvinyl alcohol, optionally of about 0.5% w / w to about 1.5% w / w, such as about 1% 20 w / w, polyvinyl alcohol.176.The travoprost particles according to any one of claims 171 to 175, wherein the first solution is an organic solution of travoprost: and the biodegradable polymer and wherein the organic solvent is evaporated and extracted during hardening the travoprost particles, optionally wherein the organic solvent is 25 dichloromethane.177 Jhe travoprost particles according to any one of claims 171 to 176, wherein hardening the travoprost particles is carried out for at least about 12 hours or tor at least about 16 hours or from about IB hours to about 24 hours, optionally wherein hardening is carried out under stirring and / or a nitrogen sweep.30178.The travoprost particles according to any one of claims 172 to 177, wherein the hardened travoprost particles are purified by centrifugation, tangential flow flitration, or a combination thereof, optionally whereto the hardened travoprost particles are purified by tangential flow filtration, further optionally wherein purifying the hardened travoprost particles concomitantly concentrates the hardened travoprost 35 particles.179.The travoprost particles according to any one of claims 173 to 178, wherein drying the travoprost: particles comprises or consists of lyophilizing the travoprost particles.180.A method of manufacturing travoprost partides, wherein the travoprost partides are a mixture of travoprost and a biodegradable polymer and wherein the method comprises a membrane emulsification step.5 181.A method of manufacturing travoprost partides, wherein the travoprost partides are a mixture oftravoprost and a biodegradable polymer and wherein the method comprises:-providing or preparing a first: solution comprising travoprost and the biodegradable polymer, -providing or preparing a second solution, wherein the second solution 1$ an aqueous solution, and-passing the first solution through a membrane with pores into the second solution to provide the travoprost10 particles, optionally wherein the membrane pore size is from about 2.5 pm to about 7.5 pm, such as about5 pm.182,A method of manufacturing travoprost particles, wherein the travoprost partides are a mixture of travoprost and a biodegradable polymer and wherein the method comprises:15 -providing or preparing a first solution comprising travoprost and the biodegradable polymer,-providing or preparing a second solution, wherein the second solution is an aqueous solution, -passing the first solution through a membrane with pores into the second solution to provide the travoprost particles, optionally wherein the membrane pore size is from about: 2..5 pm to about 7,5 pm, such as about 5 pm, and20 -hardening the travoprost particles.183.A method of manufacturing travoprost particles, wherein the travoprost particles are a mixture of travoprost: and a biodegradable polymer and wherein the method comprises:-providing or preparing a first solution comprising travoprost and the biodegradable polymer,25 -providing or preparing a second solution, wherein the second solution is an aqueous solution,-passing the first solution through a membrane with pores into the second solution to provide the travoprost particles, optionally wherein the membrane pore size is from about 2.5 pm to about 7.5 pm, such as about 5 pm, -hardening the travoprost particles, and30 -purifying the hardened travoprost particles.184.A method of manufacturing travoprost particles, wherein the travoprost particles are a mixture of travoprost and a biodegradable polymer and wherein toe method comprises:-providing or preparing a first solution comprising travoprost and toe biodegradable polymer,35 -providing or preparing a second solution, wherein the second solution is an aqueous solution,-passing toe first solution through a membrane with pores into the second solution to provide the travoprost particles, optionally wherein toe membrane pore size is from about 2.5 pm to about 7.5 pm, such as about 5 pm,■■hardening the travoprost particles,-purifying the travoprost particles, and drying the travoprost: partides,5 185,The method of any one of claims 181 to 1.¾. wherein the first solution is an organic solution of travoprostand the biodegradable polymer, optionally wherein the organic solvent is dichloromethane and / oroptionally wherein the concentration af the biodegradable polymer in the first solution is from about 30 % w / v to about <5% w / v, such as about 35% w / v, anti the concentration of travoprost in the first solution is 10 from about 20% to about 35% w / v, such as about 25% to about 30% w / v, or wherein the concentration ofthe biodegradable polymer in the first solution is from about 20 % w / v to about 45% w / v and the concentration of travoprost in the first solution is from about 40 % to about 65% w / v, such as about 50% w / v.15 186.1 he method of any one of claims 181 to 185, wherein the second solution is an aqueous solution ofpolyvinyl alcohol, optionally of about 0.53¾ w / w to about 1.5% w / w, such as about 1% w / w, polyvinyl alcohol.187,The method of any one of claims 182 to 186, wherein the first solution is an organic solution of travoprost 20 and the biodegradable polymer and wherein the organic solvent is evaporated and extracted duringhardening the travaprost particles, optionally wherein the organic solvent is dichloromethane,188,The method of any one of claims 182 to 187, wherein hardening the travoprost particles is conducted for at least about 12 hours or for at least about 16 hours or from about 18 hours to about 24 hours, optionally25 wherein hardening is carried out under stirring and / or a nitrogen sweep.189-The method of any one of claims .183 to 188, wherein the hardened travoprost particles are purified by centrifugation, tangential flow filtration, or a combination thereof, optionally wherein the hardened travoprost particles are purified by tangential flow filtration, further optionally wherein purifying the 30 hardened travoprost particles concomitantly concentrates the hardened travoprost particles,IW.The method of any one of claims 184 to 189, wherein drying the travoprost particles comprises or consists of lyophilizing the travoprost particles.35 19i.The method of any one of claims .180 to 190, wherein the biodegradable polymer is defined as in any one of claims 128 to 168 or wherein the travoprost particles are defined as in any one of claims .128 to 168.192>Travoprost particles obtainable by or obtained by the method according to any one of claims 180 to 191,193.A method of manufacturing a travoprast sustained release biodegradable intracameral implant, the method comprising:-preparing or providing travaprost partides according to any one of claims 128 to 168 or 192,-preparing a precursor mixture of an electrophilic group-oontainlng multi-arm polyethylene glycol precumor5 and the travaprost partides..-crosslinking the precursor mixture using a nucieophilk. group-contetning crosslinking agent to form a polymer network, thereby obtaining a biodegradable hydragel comprising the polymer network, wherein the travoprost particles are dispersed in the biodegradable hydrogel, and-drying the biodegradable hydrogel to provide the implant.10 194.A method of manufacturing a travoprost sustained release biodegradable intracameral implant, the methodcomprising:-preparing travoprost particles according to the method of any one of claims 128 to 168 or 192,-preparing a precursor mixture of an electrophilic group-containing multi-arm polyethylene glycol precursor and the travoprost particles,15 -crosslinking the precursor mixture using a nucleophilic group-containing crosslinking agent to form apolymer network, thereby obtaining a biodegradable hydrogel comprising the polymer network, wherein the travoprost. particles are dispersed in the biodegradable hydrogel, and-drying the biodegradable hydrogel to provide the implant.20 195. The method of claim 193 or 194, wherein the electrophilic group-containing multi-arm polyethylene giycolprecursor and / or the nucleophilic group-containing crosslinking agent are defined as in any one of claims 94 to 104,196,4 travoprost sustained release biodegradable Intracameral implant obtainable by or obtained by the25 method of any one of claims 193 to 195.197.A method of treating an ocular disease in a subject in need thereof comprising inserting an intracameral implant according to any one of claims 1 to 125 and 196 into an eye of the subject tn need of treatment,30 1.98.A method of treating glaucoma in a subject in need thereof comprising Inserting an intracameral implantaccording to any one of claims 1 to 125 and 196 Into an eye of the subject in need of treatment.199.A method of reducing the intraocular pressure in a subject with glaucoma comprising inserting anIntracameral implant according to any one of claims 1 to 125 and 196 into an eye of the subject in need of 35 treatment.200,The method of claim 198 or 199, wherein glaucoma is open angle glaucoma, optionally mild, moderate, or severe open angle glaucoma.201.A method of treating ocular hypertension in a subject in need thereof comprising inserting an intracameral implant according to any one of claims 1 to 125 and 196 into an eye of the subject in need of treatment.202.A method of reducing the intraocular pressure in a subject with ocular hypertension comprising inserting an 5 intracameral implant according to any one of claims 1 to 125 and 196 into an eye of the subject in need oftreatment.2O3.The method of any one of claims 197 to 202, wherein the intracameral implant is inserted within the iridocorneal angle of the anterior chamber of the eye of the subject in need of treatment.10204.The method of any one of claims .197 to 203, wherein the method comprises inserting one single intracameral implant per eye.205.The method of claim 204, wherein the treatment period with one single intracameral implant is about 1 to 15 about 24 months, about 3 to about 12 months, about 6 to about 12 months, about 8 to about 10 months,or at least about 9 months.206,The method of claim 204, wherein the treatment period with one single intracameral implant is about 4 months or longer, or at least about 4 months, or about: 4 months.20207.The method of any one of claims 197 to 206, wherein after a first treatment period wit!'! a first intracameral implant, at least once a new intracameral implant is inserted that provides for a further treatment period, optionally wherein the new intracameral implant is an intracameral implant according to any one of claims 1 to 125 and 196, and further optionally wherein the new intracameral implant is the same as the25 intracameral implant inserted for the prior treatment period.208.The method of claim 207, wherein the treatment is continued until no further treatment is required.209.The method of any one of claims 197 to 208, wherein the intracameral implant provides for a sustained30 release of travoprost into the aqueous humor.21O.The method of any one of claims 197 to 209, wherein the subject is a human.2ll,The intracameral implant according to any one of claims 1 to 125 and 196 for use as a medicament.35212.The Intracameral implant according to any one of claims 1 to 125 and 196 for use in a method of any one of claims 197 to 210.213.Use of the intracameral implant according to any one of claims 1 to 125 and 196 in the manufacture of a40 medicament.214,Use of the intracameral implant according to any one of claims 1 to 125 and 196 in the manufacture of a medicament for a method of any one of ciaims 197 to 210.215.A method of treating an octMar disease in a subject in need thereof comprising administering the travoprost 5 particles according to any one of ciaims 128 to 179 and 192 into an eye of the subject in need oftreatment.216.A method of treating glaucoma in a subject in need thereof comprising administering the travoprost particles according to any one of claims 128 to 179 and 192 into an eye of the subject in need of 10 treatment.217.A method of reducing the intraocular pressure in a subject with glaucoma comprising administering the travoprost particles according to any one of claims 128 to 179 and 192 into an eye of the subject in need of treatment.15218.Tbe method of claim 216 ar 217, wherein glaucoma is open angle glaucoma, optionally mild, moderate, or severe open angle glaucoma.219.A method Of treating ocular hypertension in a subject in need thereof comprising administering the 20 travoprost particles according to any one of claims 128 to 179 and 192 into an eye of the subject in needof treatment.
220. A method of reducing the Intraocular pressure in a subject with ocular hypertension comprising administering the travoprost particles according to any one of claims 128 to 179 and 192 into an eye of the 25 subject in need of treatment.221.The method according to any one of claims 215 to 220, wherein the subject is a human.222.Use of the travoprost particles according to any one of claims 128 to 179 and 192 in the manufacture of a 30 medicament.223.Use of the travoprost particles according to any one of claims 128 to 179 and 192 in the manufacture of a travoprost sustained release biodegradabie intracameral implant.35 224.Use of the travoprost particles according to any one of claims 128 to 179 and 192 In the manufacture of amedicament for a method of any one of claims 215 to 221.225.The travoprost particles according to any one of claims 128 to 179 and 192 for use as a medicament.40 226,The travoprost partides according to any one cf claims 128 to 179 and 192 for use in a method of any oneof claims 215 to 221.