Compositions and methods for treating ocular diseases

Abstract

The present disclosure relates to a travoprost sustained release biodegradable intracameral Implant comprising a biodegradable hydrogel and travoprost particles. The present disclosure also relates to travoprost particles optionally obtained by or obtainable by a process comprising a membrane emulsification step. The present disclosure also relates to a method of manufacturing travoprost particles, optionally 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 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.

Description

COMPOSITIONS AND METHODS FOR TREATING OCULAR DISEASESTECHNICAL FIELD

[0001] The present disciosure relates to a travoprost sustained release biodegradable intracameral implant comprising a biodegradable hydrogel and travoprost particles. The present disclosure also relates to travoprost particles, optionally obtained by or obtaintable by a process comprising a membrane emulsification step. The present disclosure also relates to a method of manufacturing travoprost particles, optionally 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 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, S., T., Ophthalmic Formulations. Glaucoma Today Supplement to Advanced Ocular Care, 2010; The Eye Disease Prevalence Group., Prevalence of open-angle glaucoma among adults in the United States. Arch Ophthalmol, 2004. 122: p, 532- 538), In fact, glaucoma has been reported to be one of the leading causes of irreversible blindness, and worldwide it is the second leading cause cf blindness (Quigley, H.A, and A.T. Branan, The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol, 2006. 90(3): p. 262-7). Some have projected that by the year 2040 more than 110 million people would be diagnosed with glaucoma (Tbam, Y.-C., et al., Global Prevalence of Glaucoma and Projections of Glaucoma Burden through 2.040. 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 loss 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 open anterior drainage angles and elevated intraocular pressure (IOP).

[0004] Elevated fluid pressure within the eye (i.e., 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 optic nerve (glaucoma).

[0005] For both 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 fieid ioss.Grogs that are classified as grostag fandins have been shown to effectively lower IQP (AAQ, Glaucoma Preferred Practice Pattern. 2015). The Preferred Practice Paterns of the AAO recommend prostaglandins as the first line of therapy for POAG and OHT. The most commonly prescribed topical medications for the treatment of glaucoma in the United States are the prostaglandin analogues.

[0006] Travoprost is an example of a suitable synthetic prostaglandin F2u analogue, Rs chemical name is (isopropyl (Z)-7- [(lR,2R,3R,5S)-3,5-dihydroxy-2-[(lE,3R)-3-hydroxy-4-[(a,«,<x-trifi!joro~m~isopropyl-tolyl)oxy]-l- butenyl]-cyclopentyl]-5“heptenoate. This prodrug is a synthetic prostaglandin analogue that is enzymatically converted to a free acid form in human cornea (Al-Jazzaf, A.M., L. DeSantis, and P.A. Zetland, Travoprost; a potent ocular hypotensive agent. Drugs Today (Bare), 2003. 39(1); p. 61-74). Travoprost free acid like all prostaglandins Is a selective FP prostanoid receptor agonist which is believed to reduce intraocular pressure by increasing trabecular meshwork and uveosclera! outflow (Um, K.S., et al, Mechanism of action of bimatoprast, iatanoprost, and travoprost In healthy subjects. A crossover study. Ophthalmology, 2008. 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).

[0007] Travoprost is the active ingredient In Travatan®, Travatan Z®, and Izba’* (all Alcon Laboratories, Inc,, ft Worth, TX), which are ail topical ophthalmic solutions 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 eyef s).

[0008] Successful treatment for glaucoma with available approved products requires daily selfadministered treatment with topical eye drops. While topical antihypertensive medication may be effective in treating glaucoma, any one of the available therapies will 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., B.A.T. Gabeft, 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). Kholdebarin, et al (Kholdebarin, R., at 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 3% of the patients who required more than one medicatian in the same eye failed to wait at least three 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 daily administration of single or multiple eye drops for the treatment of glaucoma, especially in an aging population with the disease.

[0009] The risk of potential blindness as a long-term effect increases in cases of poorly managed glaucoma, and patient compliance becomes an important issue. Studies have shown that fess than 50% of glaucomapatients continue therapy and refill prescriptions as required (Friedman, D.S., et a!,, 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 Insurance claims (Nordstrom, 8.L., et al„ Persistence and Adherence With Topical Glaucoma Therapy. American Journal of Ophthalmology, 2005. 140(4): p, 598.el-598.eli). Thus, a delivery system that would provide tong-term, 24 hour control of IOP could address a multitude of Issues and potentially delay or prevent loss of vision resulting from glaucoma for a patient.

[0010] Ultimate goals of drug delivery to the anterior segment include improving patient compliance, achieving an excellent safety profile and providing for sustained delivery over an extended period of time (Yellepeddi, VK and S. Palakurthi, Recent Advances in Topical Ocular Drug Delivery. Journal of Ocular Pharmacology and Therapeutics, 2015. 32(2): p. 67-82).

[0011] DURYSTA®, a birnatoprost intracameral implant approved by the FDA, is indicated for the reduction of intraocular pressure In patients with open angle glaucoma or ocular hypertension. The implant is limited to a single implant, per eye without retreatment due to possible cornea! endothelial cell loss and cornea! adverse reactions and should be used with caution in patients with narrow angles or anatomical angle obstructions. Efficacy was evaluated in two muiticenter, randomized, parailel-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 a mean baseline intraocular pressure of 24.5 mmHg. The data shew a raise in intraocular pressure for the DURYSTA group above the timolol group after week 12. DURYSTA® is an intracamera! implant containing 10 pg of blmatoprost, in a solid polymer sustained -release drug delivery system. The drug delivery system consists of poly (D,L-lactide),, poly (D,l-lactide-co~g!ycolide), poly (D,L-lactide) acid end, and polyethylene glycol 3350. Reference is made to the DURYSTA prescribing information.SUMMARY OF THE DISCLOSURE

[0012] 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 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 μm to about 19 μm as determined by laser diffraction.

[0013] In another aspect, the present disclosure is directed to a kit comprising an intracamerai implant of the present disclosure and an injection device for intracamerai injection of the intracamerai implant.

[0014] in yet another aspect, the present disclosure is directed to a syringe for intracamera! injection, wherein the syringe is loaded with an intracamerai implant according to the present disclosure.[000015] 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 μm to about 19 μm 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.

[0016] In yet another 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.

[0017] In yet another aspect, the present disclosure is directed to a method of manufacturing a travoprost sustained release biodegradable intracamerai 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 travoprost sustained release biodegradable intracamerai implant, the method comprising:-preparing or providing travoprost particles of the present disclosure,-preparing a precursor mixture of an electrophilic group-containing multi-arm polyethylene glyco! precursor and the travoprost particles,-crosslinking the precursor mixture using a nucleophilic group-containing crosslinking agent to form a polymer 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.

[0018] 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 intracamerai implant of the present disclosure 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 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 tor preservative free treatment of human subjects.

[0019] In yet another aspect, the present disclosure is directed to a method of redcing the intraocular pressure in a subject with ocular hypertension or glaucoma, such as open angle glaucoma, comprising inserting an intracamerai impiant of the present disclosure 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 someembodiments, the subject is a human. Said methods of the present disclosure have the potential for preservative free treatment of human subjects.[000020] in some aspects, the present disclosure is also directed to micropartides with alternative active ingredients than travoprost, such as other prostaglandin analogues. Examples of other prostaglandin analogues are 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 μm to about 19 μm as determined by laser diffraction. In some embodiments, the present disclosure is thus also directed to tafluprost particles, wherein the tafluprost particles are a mixture of tafluprost and a biodegradable polymer and wherein the tafluprost particles have a median diameter of about 2 μm to about 19 μm as determined by laser diffraction. In some embodiments, the present disclosure Is thus also directed to iatanoprost particles, 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 μm to about 19 μm as determined by laser diffraction. In some aspects, the present disclosure is thus also directed to corresponding sustained release biodegradable intracameral implants comprising a biodegradable hydrogel and such alternative prostangiandin analogue particles, including bimatoprost particles, tafluprost particles, or Iatanoprost particles.

[0021] The travoprost particles according to certain aspects of the present disclosure show a comparably small median particle diameter (see, for instance, also th® experimental data in Example 1), When applied in travoprost sustained release intracameral implants,, said travoprost particles according to the present disclosure provide for a desirable release profile of travoprost, which Is, in some embodiments close to linear release and / or zero-order release when measured to vitra. In some embodiments, the intracameral 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 in v / trofw 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, the intracameral implants of the present disclosure only show a limited burst at the beginning of themeasurements (such as a burst of below about 20% at Day 1). See, for instance, also the experimental data in Examples 2 and 3.

[0022] Surprlsingily, the desirable release profile of travoprost when measured under in vfav conditions can be obtained with an intracameral implant comprising only one single travorpost particle type (In some embodiments, the one single travoprost particle type contains a biodegradable polymer, such as a polylactide, having a specific inherent viscosity). In embodiments where only a single travoprost particle type is applied per implant (compared to a biend 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 unifortn final implant product. 5ee, for instance, also the experimental data in Examples 2 and 3.

[0023] Smaller particles may be beneficial due to properties such as flow kinetics within the hydrogel precursor solution and / or the increased total number of microparticles per unit volume, creating a simpler and more straightforward process to fabricate into implants, which may yield a more uniform final product with a comparable release profile than implants with different particle types containing a larger particle diameter. Additionally, due to 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, tor example, .also the experimental data in Examples 1 to 3.

[0024] The travoprost particle manufacturing process according to the present disclosure comprising a membrane emulsification step provides for a high particle yield (in some embodiments, yields of over 70%), Moreover, uniform particles can be produced. As shown herein (reference is made in particular to Example 1), membrane emulsification allows tor a narrow particle size distribution as well as the capability to fabricate microparticles of smaller diameter in higher yield than possible by other microparticie production processes, such as homogenization. Moreover, the travoprost-loaded microparticles produced by the method of the present disclosure have a smooth and spherical morphology (see also the SEM images referred to in Example 1). Also for producing comparably larger particle size diameters (such as about 20 to about 55 μm 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,

[0025] The various aspects and embodiments of the present disclosure are further described herein, in particular, in the detailed description below.BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 Schematic overview of travoprost particle production process including a membrane emulsification step [process flow diagram including AXF-Mini).

[0027] Figure 2 Schematic overview of microparticles with PLA and travoprost.

[0028] Figure 3 Particle size distribution (PSD) of travoprost loaded PLA microparticles produced with 4A PLA as measured by laser diffraction (AXF-Minl),

[0029] Figure 4A Scanning electron microscopy (SEM) images of travoprost -loaded PLA micropartides produced with 4A PLA (AXF-Minl),

[0030] Figure 4B SEM images of implants containing only one single type of travoprost-loaded PLA micrapartides produced with 4A PLA (AXF-Mlni). Implants are shown from end and side view.(00031] Figure 5 PSD of travoprost-loaded PLA microparticles produced with 7A PLA as measured by laser diffraction (AXF-Mini).

[0032] Figure 6A SEM images of travoprost-loaded PLA microparticles produced with 7A PLA (AXF-Mini).

[0033] Figure 6B SEM images of implants containing only one single type of travoprost-loaded PLA micropartictes produced with 7A PLA (AXF-Mini). Implants are shown from end and side view.

[0034] Figure 7 PSD of travoprost-loaded PLA micropartictes produced with 9A PLA as measured by laser diffraction (AXF-Mini).

[0035] Figure 8A SEM images of travoprost-loaded PLA microparticles produced with PA PLA (AXF-Mini).

[0036] Figure 8B SEM images of implants containing only one single type of fravoprost-loaded PLA microparticles produced with 9A PLA (AXF-Mini). Implants are shown from end and side view.

[0037] Figure 9 PSD of travoprost-loaded PLA microparticles produced with 5.5E PLA as measured by laser diffraction (AXF-Mini).

[0038] Figure 10A SEM images of travoprost-loaded PLA microparticles produced with 5.5E PLA (AXF- Mini).

[0039] Figure 108 SEM images of implants containing only one single type of travoprosfr loaded PLA micropartictes produced with 5.5E PLA (AXF-Mini). Implants are shown from end and side view.

[0040] Figure 11 PSD of travoprost-loaded PLA micropartictes produced with 4A PLA as measured by laser diffraction (LDC-1).

[0041] Figure 12 PSD of travoprost-loaded PLA micropartictes produced with 9A PLA as measured by laser diffraction (LDC-1 }.

[0042] Figure 13 PSD of travoprost-loaded PLA micropartictes produced with 5.5E PLA as measured by laser diffraction (LDC-1).

[0043] Figure 14 In wtro travoprast release at 37®C from implants containing only one single type of travoprost-loaded PLA microparticles produced with 4A, 7A, 9A, or 5.5E PLAfrespectively (produced with AXF-Mini; D59 of the particles is about 8 to 9 μm; see also Figures 3 to 10). Release media was lx PBS with 0.5% PEG-40 hydrogenated castor oil and 0.01% sodium fluoride. The spike at Day 7 is atributed to a sampling error.

[0044] Figure 15 A? wtetravoprast 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; D50 ofthe partides is about 10 to 13 μm; .see also Figures 11 to 13). Release media was lx PBS with 0.5% PEG-40 hydrogenated castor oil and 0.01% sodium fluoride.

[0045] Figure 16 / ft wftotravoprost release at 4O';,C from implants containing only one single type of travoprost-foaded PLA microparticles produced with 4A, 9A, or 5.5E PLA, respectively (produced with LDC-1; 050 of the particles is about 10 to 13 μm; see also Figures 11 to 13). Release media was lx PBS with 0.5% PEG-40 hydrogenated castor oil and 0.01% sodium fluoride.

[0046] Figure 17 / ft wbv travoprost release at 37eC from implants containing one single type of travoprost- loaded PLA microparticles produced with 4.A or a blend of different types of travoprost-loaded PLA microparticles produced with 4A and 7A; 4A, 7A, and 9A; and 4A, 7A, 9A, and 5.5E PLA (average particle size is about 20 to 53 μm 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.

[0047] Figure 18 Syringe assembly suitable for administering an implant of the present disclosure.DEFINITIONS

[0048] 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.

[0049] Ail documents cited and referred to herein are herewith incorporated by reference in their entirety.[OOOSO] 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 the precision of the measuring equiμment.

[0051] As used herein, the singular forms “a," "an," and "the" include plural references unless the context clearly indicates otherwise.

[0052] 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".

[0053] Open terms such as "include," "including," "contain," "containing" and the like mean "comprising." These open-ended transitionai 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.

[0054] The term "consisting of" is a closed term. This closed-ended transitional phrase means that no further elements, method steps, or the like that are not recited can be present.

[0055] 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.

[0055] The term "intracamera! implant" as used herein (might also be referred to as "intracamerai insert") refers to an object that contains travoprost and that is suitable to be inserted to the anterior chamber of an eye, in particular, to toe 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 into 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 implant into a subject's eye, although dimensions of the impiant (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 eiiminated / biodegraded either by complete dissolution or disintegration. In the present disclosure the term "implant" is used to refer both to an implant in a hydrated (also called "swollen") state when it contains water (e.g. after the implant has been (re-)hydrated 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 Sow 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 of the Implant can be measured using a Karl Fischer coulometric method, such as shown in Example 5 below.

[0057] The term "inserted" Is interchangeably used herein with the terms "placed" or "injected" or"administered" or "implanted". For example, art 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},

[0058] The term "ocular" as used in the present disclosure refers to the eye in general, or any part, or portion of the eye (as art "ocular implant" can in principle be administered to any part or portion of the eye).

[0059] The term "biodegradable" refers to a material or object (such as the intracamerai implant according to the present disclosure) which becomes degraded in vivo, i.e., when placed in the human body. In the context ofcertain 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 w ester hydrolysis in the aqueous environment of the anterior chamber of the eye. The implant slowly softens and disintegrates, resulting tn clearance through the liquefying and clearing through aqueous humor outflow pathways.

[0060] 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 bold an amount of water while 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 It contains water (e,g, after the hydrogel has been formed in an aqueous solution, or after the hydrogel has been hydrated or (re-)hydraterf 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 tow 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".

[0061] 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-contatolng multi-arm-polymer precursor with a nucleophilic group-containing cross-linking agent.

[0062] The term 'Tiber” as disclosed herein refers to a shape that is essentially cylindrical and characterized by a diameter and a length.

[0063] The term "amorphous" refers to a polymer or polymer network, which does not exhibit crystalline structures in X-ray or electron scattering experiments.

[0064] The term "semi-crystalline" refers to a polymer or polymer network, which possesses some crystalline character, i.e., exhibits some crystalline properties in X-ray or electron scattering experiments.

[0065] 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.

[0066] 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. While other materials might be present tn the hydrogel, such as travoprost or buffers, they are not referred to as "precursors".

[0067] The parts of the precursor molecules that are still present in a final polymer network are also called "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.

[0068] 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 release". Within the meaning of the disclosure, the term “sustained release" comprises essentially constant travoprost release in vitro over a certain period of time.

[0069] 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 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 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 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.

[0070] 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 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 μm to about 13 μm.[00071.] The "particle size distribution" defines the relative amount of particles present according to size. For example, one or more of the DIO, D50, and D90 values can be reported for a particle size distribution. The DIOvalue 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 μm, dD50 = 330 μm, and D90 = 1600 μm means that 10% of the particles are smaller than 83 μm, 50% of the particles are smaller than 330 μm, and 90% of the particles are smaller than 1600 μm.

[0072] The term "laser diffraction" refers to a measurement method for a particle size distribution or one or more values (such as the D10, D50, and D90 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 distribution or one or more values (such as the D10, 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 D10, 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).: :

[0073] 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 acid 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 referred to as "poly(DL)lactide").

[0074] The term "inherent viscosity" is used tc denote a physical parameter of the polylactides (PLAs) used herein. The different molecular weight polymere 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 leter suffix designates acid (A) or ester (E) end group. When measured in 0.5 % w / v 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 .

[0075] 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 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.

[0076] 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.

[0077] As used herein, "membrane emulsification" is a method for preparing micropartides. 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 constitutes polyvinyl alcohol in water, such asRODI (reverse osmosis deionized) water. In some embodiments, the membrane pore size is from about 2.5 μm to about 7.5 μm. In some embodiments, the membrane pore size is from about 3 μm to about 7 μm. In some embodiments, the membrane pore size is from about 4 μm to about 6 μm. In some embodiments, the membrane pore size is about 5 μm. 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.

[0078] As used herein, the term "aqueous humor" refers to the liquid within the anterior chamber.

[0079] 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.

[0080] 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 (in 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 tests known to the person of ordinary skill in the art. Amounts and doses of travoprost as provided herein refer to the isopropyl ester.

[0081] The terms"subject" and”patient" may 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 like), 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.

[0082] As used herein, the term "intraocular pressure" (I0P) is the fluid pressure inside the eye.Tonometry, such as Goldmann tonometry, is generally the method eye care professionals use to determine IOP.

[0083] As used herein, the term "glaucoma" may encompass the forms 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, pseudoexfoliatjve glaucoma, traumatic 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.

[0084] 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 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.DETAILED DESCRIPTION

[0085] In the following, further aspects and embodiments of the present disclosure are described.Travoprost

[0086] In some aspects, the intracameral implants and particles of the present disclosure comprise travoprost;

[0087] The IUPAC name of travoprost is (isopropyl (Z)-7- [(lR,2R,3R,5S)-3,5-dihydroxy-2-[(lE,3R)-3- hydroxy-4-[(«,< / ,<<-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:

[0088] The conversion of travoprost to travoprost acid is shown in the below scheme:

[0089] Travoprost free acid (also referred to as fluprostenol) is a prostaglandin F2a analogue and a highly 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.

[0090] Travoprost acid (as endogenous prostaglandin F2a and other prostaglandin F2a analogues) is believed to reduce intraocular pressure by increasing trabecular meshwork and uveoscleral outflow (Lim, K.S., et al., 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).

[0091] Although travoprost is a prodrug of travoprost acid (such as latanoprost being a prodrug of 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 F2a analogues".

[0092] Travoprost as prodrug facilitates corneal penetration and affords delivery of the active carboxylic acid (travoprost acid) to the aqueous humor. The prodrug ester is believed to be hydrolyzed by esterases in the cornea to the biologically active free acid in which carbons 17-20 have been substituted with a metatrifluoromethylphenoxy group. See, for example, Al-Jazzaf, A.M., L. DeSantis, and P.A. Netland, Travoprost: a potent ocular hypotensive agent. Drugs Today (Bare), 2003. 39(1): p. 61-74).

[0093] 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. Travoprost particles

[0094] 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 μm to about 19 μm as determined by laser diffraction.

[0095] In some embodiments, the travoprost particles have a median diameter of about 3 μm to about 19 μm as determined by laser diffraction. In some embodiments, the travoprost particles have a median diameter of about 4 μm to about 17 μm as determined by laser diffraction. In some embodiments, the travoprost particles have a median diameter of about 5 μm to about 16 μm as determined by laser diffraction. In some embodiments, the travoprost particles have a median diameter of about 6 μm to about 15 μm as determined by laser diffraction. In some embodiments, the travoprost particles have a median diameter of about 7 μm to about 14 μm as determined by laser diffraction,

[0096] In some embodiments, the travoprost particles have a median diameter of about 8 μm to about 13 μm as determined by laser diffraction.

[0097] In some embodiments, the travoprost particles have a median diameter of about 7 μm to about 10 μm as determined by laser diffraction. In some embodiments, the travoprost particles have a median diameter of about 8 μm to about 9 μm as determined by laser diffraction. In some embodiments, the travoprost particles have a median diameter of about 8 μm or about 9 μm as determined by laser diffraction.:

[0098] In some embodiments, the travoprost particles have a median diameter of about 9 μm to about 14 μm as determined by laser diffraction. In some embodiments, the travoprost particles have a median diameter of about 10 μm to about 13 μm as determined by laser diffraction. In some embodiments, the travoprost particles have a median diameter of about 10 μm to about 12 μm as determined by laser diffraction. In some embodiments, the travoprost particles have a median diameter of about 12 μm to about 14 μm as determined by laser diffraction. In some embodiments, the travoprost particles have a median diameter of about 9 μm to about 11 μm as determined by laser diffraction. In some embodiments, the travoprost particles have a median diameter of about 10 μm or about 11 μm as determined by laser diffraction. In some embodiments, the travoprost particles have a median diameter of about 12 μm or about 13 μm as determined by laser diffraction.

[0099] In some embodiments, the particle size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 2 μm to about 10 μm, D50 of about 6 μm to about 15 μm,and D90 of up to about 50 μm, such as D90 of about 12 to about 26 μm. In some embodiments, the particle size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 3 μm to about 9 μm, D50 of about 7 μm to about 14 μm, and D90 of up to about 50 μm, such as D90 of about 12 to about 26 μm.[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 μm to about 9 μm, D50 of about 9 μm to about 14 μm, and D90 of about 13 μm to about 26 μm. In some embodiments, the particle size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 6 μm to about 8 μm, D50 of about 10 μm to about 13 μm, and D90 of about 14 μm to about 25 μm. In some embodiments, the particle size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 8 μm, D50 of about 12 μm, and D90 of about 15 μm. In same embodiments, the particle size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 6 μm, D50 of about 10 μm, and D90 of about 14 μm. In some embodiments, the particle size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 6 μm, D50 of about 13 μm, and D90 of about 25 μm.[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 μm to about 6 μm, D50 of about 7 μm to about 10 μm, and D90 of about 12 μm to about 16 μm. In some embodiments, the particle size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 4 μm to about 5 μm, D50 of about 8 μm to about 9 μm, and D90 of about 13 μm to about 15 μm. In some embodiments, the particle size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 5 μm, D50 of about 9 μm, and D90 of about 14 μm. In some embodiments, the particle size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 5 μm, D50 of about 8 μm, and D90 of about 13 μm. In some embodiments, the particle size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 4 μm, D50 of about 8 μm, and D90 of about 13 μm. In some embodiments, the particle size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 5 μm, D50 of about 9 μm, and D90 of about 15 μm.[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 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 someembodiments, 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 particles.[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 based 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( LJIactide . 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.[000111] 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(DL)lactide. In some embodiments, the biodegradable polymer comprises or consists of a polylactide and wherein the polylactide has an add 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, 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 a n acid end group, 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 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, the travoprost particles comprise about 44 wt-% to about 48 wt-%, such as about45 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 μm to about 6 μm, D50 of about 8 μm to about 10 μm, and D90 of about 13 μm to about 15 μm. 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 μm, D50 of about 9 μm, and 090 of about 14 μm. In some of these embodiment, the particle size distribution of said travoprost particles as determined by laser diffraction is characterized as follows: D10 of about 7 μm to about 9 μm, D50 of about 11 μm to about 13 μm, and D90 of about 14 μm to about 16 μm. 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 μm, D50 of about 12 μm, and D90 of about 15 μm.[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. In some of these embodiments, the travoprost particles comprise about 45 wt-% to about 49 wt-%, such as about46 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 μm to about 6 μm, D50 of about 7 μm to about 9 μm, and D90of about 12 μm to about 14 μm. 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 μm, D50 of about 8 μm, and D90 of about 13 μm.[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 dl / 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: D10 of about 3 μm to about 5 μm, D50 of about 7 μm to about 9 μm, and D90 of about 12 μm to about 14 μm. 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 μm, D50 of about 8 μm, and D90 of about 13 μm. 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 μm to about 7 μm, D50 of about 9 μm to about 11 μm, and D90 of about 13 μm to about 15 μm. 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 μm, D50 of about 10 μm, and D90 of about 14 μm,[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 particles. 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 μm to about 6 μm, D50 of about 8 μm to about 10 μm, and D90 of about 14 μm to about 16 μm. In some of tese embodlmeflB,;>e partde size distribution of the travoprost particles as detem^diffraction is characterized as follows: D10 of about 5 μm, D50 of about 9 μm, and D90 of about 15 μm. 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 μm to about 7 μm, D50 of about 12 μm to about 14 μm, and D90 of about24 μm to about 26 μm. 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 μm, D50 of about 13 μm, and D90 of about25 μm.[000118] In some embodiments, the travoprost particles essentially consist of the mixture of travoprost and the biodegradable polymer. The term "essentially consist of" as used herein allows for the 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 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] I n so me embodiments, the travoprost particles are obtained by or are obtainable by a process 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: -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 μm to about 7.5 μm, such as about S μm. [000122] 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 μm to about 7.5 μm, such as about 5 μm, 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 μm to about 7.5 μm, such as about 5 μm,-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: -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 μm to about 7.5 μm, such as about 5 um, -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 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 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 about50% 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.[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 / min.[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 the 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 poly(lactic 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 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 biodegradable polymer, wherein the particles have a median diameter of about 2 μm to about 19 μm, such as about 8 μm to about 13 μm, as determined by laser diffraction. In some embodiments, the biodegradable polymer comprises or consists of a polylactide, optionally with an acid or ester end group. Ir some embodiments, the prostaglandin analogue is bimatoprost. In some embodiments, the prostaglandin analogue is latanoprost In some embodiments, the prostaglandin analogue is tafluprost.Unoprostene Latanoprostene bunodMethod 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- 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: -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 partides[000138] 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,-passing the first solution through a membrane with pores into the second solution to provide the travoprost 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: -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,-hardening the travoprost particles, and-purifying the hardened travoprost particles. [000140] 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, -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. [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 μm to about 7.5 μm. In some embodiments, the membrane pore size is from about 3 μm to about 7 μm. In some embodiments, the membrane pore size is from about 4 μm to about 6 μm.[000143] In some embodiments, the membrane pore size is about 5 μm.[000144] In some embodiments, the first solution is an organic solution of travoprost and the biodegradable polymer. In some embodiments, 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 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% toabout 65% w / v, such as about 50% w / v. The first solution is commonly also referred to as the dispersed phase orDP 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 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 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, 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 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. [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 add end group or an ester end group. In some embodiments, the 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 dt / g, as measured at 0.5% w / v in chloroform at 30°C, and optionally has an add 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 25°C, 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 μm. [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 μm. In some embodiments, the biodegradable polymer of such travoprost particles consists of a polylactide having an inherent viscosity of about 0.30 to about 1.00 dL / g as determined at 0.5% w / v in CHCh at 30 °C.[000155] In some embodiments, the median diameter of the travoprost particles produced by the method of manufacturing travoprost particles is about 2 μm to about 19 μm, such as about 7 μm to about 14 μm. In some embodiments, the median diameter of the travoprost particles is about 8 μm to about 13 μm. In some embodiments, the median diameter of the travoprost particles is about 8 μm to about 9 μm. In some embodiments, the median diameter of the travoprost particles is about 10 μm to about 13 μm, such as about 10 μm, about 12 μm, or about 13 μm. 3 [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. [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 Partides").Travoprost sustained release intracameral implant[000158] The present disclosure, in a further aspect, is directed to 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 glycol, 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 μm to about 19 μm 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 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 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 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").Travoprost particules . in the intracameral implant[000162] For the travoprost particles in the intracameral implant of the present disclosure, reference is made 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 μm to about 14 μm. In some embodiments, the travoprost particles have a median diameter of about 8 μm to about 13 μm. In some embodiments, the biodegradable polymer consists of a polylactide having 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 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 "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 particlesmight thus be distinguished from each other 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, 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, 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 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] 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 0.25 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, 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 μm to about 6 μm, D50 of about 8 μm to about 10 μm, and D90 of about 13 μm to about 15 μm. 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 μm, D50 of about 9 μm, and D90 of about 14 μm. 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 μm to^about 9 μm, DSO^rfabout 11 μm to about 13 μm, and D90 of about 14 μm to about 16 μm. 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 μm, D50 of about 12 μm, and D90 of about 15 μm.[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, 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 μm to about 6 μm, D50 of about 7 μm to about 9 μm, and D90 of about 12 μm to about 14 μm. In someof these embodiments, the particle size distribution of said travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 5 μm, D50 of about 8 μm, and D90 of about 13 μm.[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 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-%, 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 3 μm to about 5 μm, D50 of about 7 μm to about 9 μm, and D90 of about 12 μm to about 14 μm. 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 μm, D50 of about 8 μm, and D90 of about 13 μm. 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 μm to about 7 μm, D50 of about 9 μm to about 11 μm, and D90 of about 13 μm to about 15 μm. 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 μm, D50 of about 10 μm, and D90 of about 14 μm.[000168] 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 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 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 μm to about 6 μm, D50 of about 8 μm to about 10 μm, and D90 of about 14 μm to about 16 μm. 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 5 μm, D50 of about 9 μm, and D90 of about 15 μm. 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 μm to about 7 μm, D50 of about 12 μm to about 14 μm, and D90 of about 24 μm to about 26 μm. 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 μm, D50 of about 13 μm, and D90 of about 25 μm.[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 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. Bieodegradable hydrogel[000171] In the intracameral implants of the present disclosure the biodegradable hydrogel comprises a 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: :wherein m isi, 2, 3, and / or 6. in some embodiments, m is 1. In some embodiments, m B2. 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. [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 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 ahigher 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 mere 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 multi-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 embodiments, the polymer network is formed by reacting a one or more units of 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 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. Insome embodiments, the visualization agent is selected from Be 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 embod ments, 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 with a visualization agent.[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, the electrophilic group-containing multi-arm 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 is8-arm-15K-PEG-SAZ.[000193] In some embodiments, the electrophilic group-containing multi-arm polyethylene glycol precursor is 8-arm-15K-PEG-SAZ and the nucleophilic group-containing cross-linking agent is a trilysine, such as a salt of trilysine, such as trilysine acetate.[000194] In some 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).:Where m is 1, each arm is terminated with a succinimidy [succinate (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 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 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: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. ; [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.[Q00197] 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 30 wt-% to about 50 wt-% or about 34 wt-% to about 42 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 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-%. [000198] In some embodiments, the total mass of the biodegradable hydrogel in the intracameral implant in its dried state is about 30 μg to about 50 μg or about 34 μg 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 μg 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 μg to about 39 μg or about 38 pg. [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 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 μg to about 260 μg or about 235 μg 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 μg to about 248 pg. In some embodiments, the total mass of the biodegradable hydrogel in the intracameral implant in its dried state is about 244 μg to about 246 μg 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 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 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 1.50 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 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 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 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 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-%, [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 wt-% or about 12 wt-% of travoprost.[000208] In some embodiments, the implant comprises a dose of about 5 μg to about 50 pg or about 10 pg to about 45 μg of travoprost. In some embodiments, the implant comprises a dose of about 10 pg to about 40 pg or about 15 μg to about 35 μg of travoprost. In some embodiments, the implant comprises a dose of about 20 pg toabout 30 μg or about 25 μg to about 30 μg of travoprost. In some embodiments, the implant comprises a dose of about 22 μg to about 30 μg or about 24 μg to about 28 μg of travoprost. In some embodiments, the implant comprises a dose of about 25 μg to about 27 μg or about 26 μg of travoprost.[000209] In some embodiments, the implant comprises a dose of about 30 μg to about 50 pg or about 35 pg to about 45 μg of travoprost. In some embodiments, the implant comprises a dose of about 36 pg to about 44 pg or about 37 μg to about 43 μg of travoprost. In some embodiments, the implant comprises a dose of about 38 pg to about 42 μg or about 39 μg to about 41 μg of travoprost. In some embodiments, the implant comprises a dose of about 40 μg of travoprost.[000210] In some embodiments, the implant is in the form of a fiber. [000211] In some embodiments, the implant has a total weight of about 50 μg to about 150 pg, or of about75 μg to about 125 μg in its dried state. In some embodiments, the implant has a total weight of about 80 pg to about 120 μg or of about 90 μg to about 110 μg in its dried state. In some embodiments, the implant has a total weight of about 95 μg to about 105 μg in its dried state. In some embodiments, the implant has a total weight of about 100 μg in its dried slate. [000212] In some embodiments, the implant has a total weight of about 300 μg to about 400 pg, or of about320 μg to about 380 μg in its dried state. In some embodiments, the implant has a total weight of about 330 pg to about 370 μg or of about 340 μg to about 360 μg in its dried state. In some embodiments, the implant has a total weight of about 345 μg to about 355 μg in its dried state. In some embodiments, the implant has a total weight of about 350 μg in its dried state. [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 witi respect to Be total weight of 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 μg to about 39 μg or about 31 μg to about 37 pg. In some embodiments, the total mass of the biodegradable polymer in the implant in its dried state is about 32 μg to about 36 μg or about 33 μg to about 35 pg or about 34 pg.[000216] In some embodiments, the total mass of the biodegradable polymer in the implant in its dried state is about 47 μg to about 57 μg or about 49 μg to about 55 pg. In some embodiments, the total mass of thebiodegradable polymer in the implant in its dried state is about 50 μg to about 54 μg 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 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 μg 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 μg to about 41 pg, such as about 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 μg 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 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 μg 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.[00022®] In some embodiments, the implant comprises a dose of about 24 μg 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 μg 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.[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 μg to about 15 pg or from about 2 pg to about 13 μg 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 pg, such as from about 11 μg to about 13 pg, sodium phosphate. In some embodiments, the implant comprises about 12 μg 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 intracamerai imptent 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 intracamerai implant comprising a biodegradable hydrogel and travoprost particles has the foilowing composition in its dried state:• about 35 μg to about 45 pg, such as about 40 pg, travoprost;• about 240 μg to about 250 pg, such as about 245 pg, biodegradable hydragel formed by reacting 8al5K PEG SAZ with trilysine acetate, optionally at a weight ratio of about 16:1;• about 50 μg to about 55 μg, such as about 52 pg, biodegradable polymer, optionally wherein the biodegradable polymer consists of pgiy(D,L)lactlde’• optionaily about 5 μg to about 7 pg, such as about 6 pg, sodium phosphate monobasic; and• further optionally about 6 μg to about 8 pg, such as about 7 pg, sodium phosphate dibasic, wherein the Implant has a total weight of about 340 μg to about 360 pg, such as about 350 pg, in its dried state.In some of these embodiments, the median diameter of the travoprost particles is about 8 μm to about 13 μm. 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 di / g to about 1.00 dl / g, as measured at 0.5% w / v chloroform at 30°C, and optionally has an acid end group. In some of these embodiments, the biodegradable polymer consists of poiylactide (such as poly(DL)lactide) having an inherent viscosity specification from about 0.45 di / g to about 0.85 di / g, such as about 0.55 di / g to about 0.75 dl / 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 intracameral implant comprising a biodegradable hydrogel and travoprost particles has the following composition in its dried state:* about 20 μg to about 30 pg, such as about 26 pg, travoprost;• about 35 μg to about 45 pg, such as about 38 pg, biodegradable hydrogel formed by reacting SalSK PEG SAZ with trilysine acetate, optionally' at a weight ratio of about 16: 1;about 30 ;.sg to about 40 pg, such as about 34 pg, biodegradable polymer, optionally wherein the biodegradable polymer consists of poly(D,L)lactlde;• optionally about 0.5 μg to about 1.5 pg, such as about 1 pg, sodium phosphate monobasic; and* further optionally about 0.5 μg to about 1,5 pg, such as about 1 pg, sodium phosphate dibasic, wherein the implant has a total weight of about 90 μg to about 110 pg, such as about 100 pg, in its dried state, and optionally wherein the 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 the travoprost particles is about 8 μm to about 13 μm. In some of these embodiments, the implant comprises only one type of travoprost particles, in some of these embodiments, the biodegradable polymer consists of polylactide (such as poly(DL)lactjde) having 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 chloroform at 30°C, and optionally has an acid end group. In some of these embodiments, the biodegradable polymer consists of poiylactide (such as poiy(DL)iactide) 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 chloroform at 25°C, 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.In t-fe? release properties of toe intracamerai implant[000227] In some embodiments, the implant shows a travoprost in vitro release of less than about: 60% or less than about 25% or less than about 28% based on the total weight of travoprost: in the intracamerai impiant afterincubating the intracamerai implant for 1 day under simulated physiological sink conditions (n 50 ml of lx PBS, 8,5% castor oil, 0.01% sodium fluoride buffer at pH ?.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 10% to about 30% or of about 15% to about 25% based on the total weight of travoprost In the Intracamerai impiant after incubating the Intracamerai 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 intracamerai impiant after incubating the intracamerai 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>[000230] In some embodiments, the implant shows a travoprost / >? wfrv 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 oil, 0,01% sodium fluoride buffer at pH 7.2-7.4 at 37 °C. [000231] In some embodiments, the implant shows a travoprost in vitro 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 7,2- 7.4 at 37 °C, [000232] In some embodiments, the implant shows a travoprost fo 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 intracamerai 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.[000233] In some embodiments, the implant shows a travoprost in vitro retease of about 40% to about 50% or of about 60% to about 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 SO 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 Imptent 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 the total weight of travoprost in the intracamerai 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.[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 intracamerai 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 85% to about 95% based on the total weight of travoprost in the intracameral implant after incubatingthe 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.[000238] 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 far 100 days under simulated physiological sink conditions in SO mL of lx P8S, 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 rnL 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 % fo 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 °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 (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 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 °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 (i.e. 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 w vitro release from the Implant when incubating the intracameral implant under simulated physiological sink conditions in SO ml of lx PBS, 0,5% castor oil, 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 travo prost sustained release biodegradable intracameral implant[000245] In a further aspect, the present disclosure Is directed to a method of manufacturing a travoprost sustained release biodegradable intracameral Implant, 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 particles,-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, the travoprost particles have a median diameter of about 2 urn. to about 1$ μm or of about 8 μm to about 13 μm 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 the 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 crosslinking agent is a trilysine, such as trilysine acetate.[000249] In some embodiments, the precursor mixture of the electrophilic group-containing multi-arm polyethylene glycol precursor and the travoprost particles 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 aboutsuch as at about 33°C. In some embodiments, drying is carried out under nitrogen flow. In some embodiments, drying is carried out for about 48 tn about 72 hours. In some embodiments, the biodegradable hydrogei is dried in a tubing.[000252] In some embodiments, the method further comprises loading the impiant 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. [000253] In some embodiments, the method further comprises loading the impiant into the needle of a syringe for intracamera! 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 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 impiant").Device for injection of the travoprost implant of the present disclosure and kit [000257] In a further aspect, the present disclosure is directed to an injection device for intracamerai injection of an impiant 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 25G needle or a 27G needle, in some embodiments, the injection device is a syringe with a 26G needie. 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 loaded with the intracamerai implant, wherein the needie is a 26G needle.[000258] In some embodiments, the injection device is a synnge 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 an intracameral implant according to the present disclosure (in particular, as defined in the section “Travoprost sustained release biodegradable intracameral implant'' above) and an 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 for 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 ocular 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 toe description above, in particular, to toe chapter “Travoprost sustained release intracameral implant”.[000281] 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".[000252] 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 toe chapter "Travoprost sustained release Intracameral impiant".[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 intracameral implant according to the present disciosure 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".[000265] 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 intracamera! implant”.[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 intracameral implant per eye. Ift some embodiments, the method comprises bilateral treatment, i.e. treatment of both eyes of a subject by inserting one single iritracameral implant in each of the subject's eyes.[000263] In some embodiments, the treatment period with one single intracameral 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 iC 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 herein. 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 fe 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 intracameral 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 intracameral implant, reference is made to the description above, in particular, to the chapter "Travoprost sustained release intracameral implant".[000276] 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. 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 intracameral implant".[000277] 10 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 partides, 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 toe 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 toe 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 toe 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 disdosure") above. As regards the travoprost particles, reference is made to the description above, in particular, to the chapter "Travoprost parbcles”.[000285] 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".[00Q286] 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 particles".[000287] In a further aspect, the present disclosure is directed to the travoprost particles 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 intrac ameral 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 thereby gets fixated tn 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 fuiiy degrades.[000290] In some embodiments, the intracamerai implant is gentle to the endothelium. Without wishing to be bound to any theory, it is beiieved that the prohibition of movement and its soft tissue-like 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 intracamerai 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 intracamerai implant is biodegradable in a residual-free manner 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] Iri some embodiments, the intracameral implant of the present disclosure provides for a long-term treatment effect[000295] In some embodiments, repeated treatment of a subject is possible with the intracameral implants of the present disclosure.[000296] In some embodiments, essentially no endothelial damage occurs following administration of the intracameral implant, In some embodiments, essentially no no change in pachymetry 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.EXAMPLES[000297] The following Examples are included to demonstrate certain aspects and embodiments of the disclosure as described in the claims. It should be appreciated by these of skill in the art, however, that the foliowing description is illustrative only and should not be taken in any way as a restriction of the disclosure.EXAMPLE 1: MANUFACTURE OF TRAVOPROST- LOADED MICROPARTICLES[000298] Ttevoprosfe-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 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 Micropore Technologies (United Kingdom) or the AXF-Minf system by Micropore Technologies (united Kingdom). The LDC-i (Micropore Technologies, United Kingdom) and the AXF-Mlni (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 LDC-1 can be referred to as an academic test unit designed to be directly scalable to Micropore AXF units.[000300] 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 (DX-lactide) (PLA) were dissolved in dichloromethane (DCM) to prepare the DP (single -phase solution).[000301] Microparticles were exemplary 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 Ort the PLA type.[000302] Microparticles were exempiariy produced with each of three types of PLA: 4A, 9A and 5.5E when using the LDC-1. The target travoprost loading was 50.0% w / v, while the PLA concentration in the DP ranged from20.6 -43.3% w / v depending on PLA type.[000303] The different molecular weight polymers are described as 4A, 7A, 9A and 5.5E PLA, wherein 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 chloroform at 30 °C, 4A PLA has an Inherent viscosity specification of 0.35 to 0.45 dl / 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 ºC, 5.5E PLA has an inherent viscosity specification of 0.55 to 0.75 dl / g. Parameters on how the inherent viscosity of poiylactidgs can be measured are set forth in Table 1 below.Table 1 Experiments! parameters for measuring the inherent viscosity of the polylactides.Production with AXF-Mini[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-clamps. The membrane is cylindrical in shape with laser-cut pores etched into the center walls. The stainless-steel insert fits within the membrane and defines the distance between the inner diameter of the membrane and the outer diameter of the insert; this region is where particle formation occurs. The CP inlet tubing enters the AXF-Mini through the cylindrical membrane / insert, white the DP inlet enters perpendicularly through the membrane pores.[000305] 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 / mln, while the CP was set from 70-80 ml / inin (smaller particlesize 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 partides were stirred overnight in the quench vessel to harden the microparticles and extract and evaporate excess DCM. Once the partides had stirred tor > 16 hours, they were cleaned and concentrated using tangential flow filtration (TFF). The cleaned 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 stainiess-steei membrane that is seated in the base of the LDC-1. 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 μm pores was utilized while the flow rate of the DP solution into the LDC-1 was maintained at Q.125 mL / mln, and the agitation setpoint for the overhead stirrer was maintained at ISV. 3mL of DP solution was injected into the LDC-1 sampling chamber to maintain a 54; 1 CPiDP ratio by volume. Once the injection was complete, die 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 micropartictes have been quenched for 18 - 24 hours, they were cleaned from the CP solution and concentrated using centrifugal methods. The cleaned microparticles were then lyophilized to remove af I water and yield a dry powder.[000310] Once the microparticles produced using the (DC-1 dr AXF-Mini, respectively,, were dried, they were imaged by scanning electron microscope (SEM), partide size distribution was determined by laser 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 Mastersiser 3000E. 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.Table 2 Parameters for particle size distribution (PSD) measurement.[000312] Once settings were confirmed, the small volume sample dispersion unit was filled with RODI water. The dispersion unit controller was set to ~1000 rμm. 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 analysts by adding ~5 mg of microparticles to a 2 ml Eppendorf tube 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 10 sample measurements were then taken and DIO, D50, 090, and 099 (μm) were reported.M icroparticies prod need by AX[000313] Exemplary formulation and process parameters for die AXF-Mirti to yield particles of smaller diameter are summarized in Table 3 betow. The resultant particles had a particle size distribution of DIO ~ 4.61 μm;D50 = 7.89 μm; D90 = 12.84 μm 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-618- 078.* T ravoprost load = (amount of travoprost) / [(amount of travoprost) + (amount of PLA)] QS ~ quantity sufficient.[000314] Further micropartfcles were prepared by membrane emulslficatior! (AXF-Mini) as described above,Sfee Table 4 for further details.Table 4 Information on different travoprost partides produced by AXF-Mint (including specific mieroparticfe lot number).3Travoprost content is per formulation notebook record, not measured. Given on dry basss of final microparticles. [000315] The particie size distribution (PSD) of tfavoprost-ioaded microparticles comprising 4A PLA (tot No,MP-695-078) is shown in Figure 3. Corresponding scanning electran microscopy (SEM) images of the travoprost- loaded microparticles comprising 4A PLA are shown In Figure 4A.[000316] The partide size distribution (PSD) of tfavoprost-ioaded mieropartides comprising 7 A PLA (Lot No.MP-618-078) is shown in Figure 5. Corresponding scanning electron microscopy (SEM) images of the travoprost- loaded fnicropartides comprising 7A PLA are shown in Figure 6A,[000317] The partide size distribution (PSD) of travoprost-loaded micropartides comprising 9A PLA (Lot No. MP-695-082) is shown in Figure 7 Corresponding scanning electron microscopy (SEM) images of the travoprast- ioaded microparticles comprising 9A PLA are shown in Figure BA.[000318] The particle size distribution (PSD) of travoprost-loaclecl micropartides 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 ISA. [000319] The PSD of aii travoprost-loaded micropartddes was narrow. Moreover, the travoprost-ioaded microparticles were shown by the. SEM images to have a smooth and spherical morphology. Microparticles produced by LDC-1[000320] Table 5 provides information on different microparticles produced with the LDC-1. Table 5 Information on different travoprost particles produced by LDC-1 (including specific micropartide tot number).[000321] The particle size distribution (PSD) of travoprost-loaded micropartides comprising 4A PLA (Lot No.MJS77-187) is shown in Figure 11. The partide size distribution (PSD) of travoprost«loaded microparticles comprising 9A PLA (Lot No. MJ577-177) is shown in Figure 12. The particle site distribution (PSD) of travoprost- loaded micropartides comprising 5.5E PLA (Lot No. MJ577-183) is shown in Figure 13. [000322] The PSD of all travcsprost*loaded micropartddes was narrow,Microparticues with larger[000323] The AXF-Mini can also be applied to produce micropartides with a higher median partide size diameter. Exampie formulation and AXF-Mini process parameters to yield partides with a larger size (comparable tomicroparticles in the size range of 20-53 μm that can be obtained by homogenization followed by sieving) are summarized in Table 6 below. The resultant particles had a particle size distribution of DIO 30.7 μm; D50 37.3 μm- D90 = 45,1 gm as measured by Malvern Mastersizer 3000E, To achieve this PSD, particles 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).*Travoprost load = (amount of travoprost) / [(amount of travoprost) + (amount of Pi A)} QS ■" quantity sufficient.[000324] The travoprost -loaded microparticles described herein were applied in the manufacturing of ocular implants (see Example 2),EXAMPLE 2: MANUFACTURE OF TRAVOPROST-CONTAINING IMPLANTS[000325] In the following, travoprost-loaded microparticles, in particular the microparticles as described inExample 1, were casted into ocular implants. For the smaller particle sizes, only one type of travoprost-loaded microparticle was used in each implant formulation. General procedure [000326] The freeze-dried microparticles (4A, 7A, 9A and / or 5.5E, 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 particleswere suspended ih water for Injection (WF1). 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 into a small ID tubing (such as 0.4 mm or 0.5 mm tubing ID).Preparafion.pf Trilysine Acetate (TLA) $0tetteB.§tflilSyriagg[000327] The amount of Trilysine Acetate (TLA) was calculated based ort 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 foe solution was measured and recorded. A pre-defined volume was pipeted 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 Mtcropartjcle Svnnue[000328] After the microparticles 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 the suspension.Preparation of f-'EG Syringe[000329] A predefined amount of 8al5k PEG was weighed and transferred to a syringe. Sodium PhosphateMonobasic solution was pipeted into the syringe to dissolve BalSk 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 degassing of the solution.Casting[000330] For each run a micropartide syringe and PEG syringe were connected by a female to female luer connector. Sow 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 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. Stow even pressure was used to pass the contents of each syringe back (i pass) and forth (1 pass) for total 25 -50 times to create the PEG / microparticle^LA suspension. The suspension was drawn Into one syringe and primed to remove any excess air.[000331] While the suspension was still in liquid form, toe syringe is connected to tubing and the suspension was injected into the tubing. Once the tubing was full, it is capped on the botom end, detached from the syringe and capped at the casting end. The remaining pieces of tubing were filled in the same manner until the gel sets.[000332] Once all 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 (ite,, 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 %. 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 the removal process were discarded. The strands were fed into a cutter that cut the strand into approximately 2.8 mm long implants. During the cuting 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.Determination of the travobrest content[000335] The travoprest 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 mi of acetonitrile was added, and the flask was sonicated for -'- I 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 pg / m! serially diluted to ~5.0 pg / ml using a diluent of 70:30 water:acetonlfriie. The samples were run on a Waters UPLC with the setings shown in Table 7. Table 7 UPLC setings for travoprost content determination.[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.[000337] implant formulations 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 μg values given on dry basis).[000338] The microparticle load as well as measured travoprost content for corresponding implants is given in Table 9.Table 9 Mesured travoprost amount and microparticle load.* 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. Table 10 Mesured travoprost amount, dimensions, and implant weights.’Values are the average of 10 implants.[000340] The implants were inspected by scanning electron microscopy (SEM). Fig. 48 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 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 5.5E PLA). Overall, all implants had a uniform appearance. Examplary implan forulation containing microparticules producedwith LDC-1[000341] Implant formulations of the present disclosure with one single particle type (smaller particle diameter) are shown in Table 11.Table 11 Nominal (theoretical, not measured) implant formulation (% and μg values given on dry basis).[000342] Table 12 shows properties of representative implant batches.Table 12 Microparticle load, dimensions, and implant weights.‘Values are the average of 12 implants.* 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 load is defined as the sum of PLA mass concentration (%w / w) and travoprost mass concentration (%w / w).EXAMPLE 3: IN VITRO RELASE MEASUREMENTS[000343] The in vitro release from travoprost-containing implants produced as in particular described under Example 2 was measured in the following.[000344] M wlfirp release measurements were performed under simulated ftiysiological sink conditions using15 implants in 50 mL of lx PBS, 0.5% polyoxyl 40 hydrogenated castor oil, 0.01% sodium fluoride buffer at pH 7.2-7.4 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 C18 reversed-phase column using ultra high-performance liquid chromatography with UV detection at 220 nm.;sevitrorelease from i containing minse mpa lants[000345] In vitro release at 37°C of travoprost from the implants containing microparticles produced withAXF-Mini (formulated according to Table 8; with one single smaller diameter travoprost particle type per implant) is shown in Figure 14.[000346] In vitro release at 37°C of travoprost from the implants containing microparticles produced withLDC-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 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.[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.[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 microparticle 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.[000351] Surprisingly, an implant containing a single type of smaller size travoprost-loaded 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 microparticles (4A, 7A, 9A, and 5.5E PLA). See, for 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 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.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.2.0SC»PEThis 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 DepotsProtocol / RePort:5.0 EQUIPMENT SET-UPSet up the portable glovebox per SOP-10053 Gloveboxes. Ensure flow meter is siting 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 least ~2-3 psi. This is "full flow" nitrogen. Purge the glovebox at full flow forat least 30 minutes.Refer to SOP-10080 Kart Fischer Coulometer with 874 Oven Sample Processor using Tiamo Software for instrument set up and analysis procedure.6.0 BLANK PREPARATIONBenchtop Blank preparation - perform in triplicate (n=3) - System SuitabilityBlanks;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.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 Blanks6.2.1 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.6.2.3 Place vial in the autosampler.6.2.4 Analyze blanks for water content according to Section 9.0.7.0 STANDARD PREPARATIONWater standard preparation - perform in triplicate (n=3)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 SOP-10050 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 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 preparation7.2.2 Equilibrate an empty vial on benchtop conditions for at least 30 minutes.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.7.2.5 Analyze standards for water content according to Section 9.0.8.0 SAMPLE PREPARATIONSOTX-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.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 of5 minutes. i; ;i8.1.5 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. :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.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 ambientconditions of the instrument.9.0 ANALYSIS PROCEDUREProcedural References 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. 9.2 Ensure that the Karl Fischer Titrator with oven sample processor system is set to the following parameters:♦Note: The KF Blank and System Suitability Blank methods use an extraction time of 60 seconds.Common variables9.3.1 Two common variables are required in the Tiamo 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. 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 injections.; ;CNote: For a summary of the common variables used, see the table below:: teLEiS£ta_Analysis9.4.1 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 freshly crimped empty vials. Run system preparation at the start of every run using the "KF System Prep" method inTiamo.Note: If freshly crimped empty vials9.4.2 Make one injection of each system suitability blank vial (n=3) using the "System Suitability Blank" method inTiamo. , fr fr:c9.4.3 Make one injection of each water standard vial (n= 3) using the "KF Benchtop Standard" method in Tiamo. 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:System SgiiahLM9.6.3.1 The bracket standard percent recovery must fall in the range of 95.0 - 105.0%.10.0 SAMPLE CALCULATIONS 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% ". 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 PRESENTDISCLOSURE[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. [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 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 seal 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 H?O. Use of the bubble emission test to support the 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.

Claims

CLAIMSWhat is claimed is:

1. A travoprost sustained release biodegradable intracameral implant comprising a biodegradable hydrogel and travaprost particles, wherein the biodegradable hydrogel comprises a polymer network comprising one or more units of polyaikylene 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 μm to about 19 μm as determined by laser diffraction,2. The intracameral implant according to claim 1, wherein the travoprost partlcies have a median diameter of about 4 μm to about 17 μm or about 5 μm to about 16 μm as determined by laser diffraction.

3. The intracameral implant according to claim 1, wherein the travoprost particles have a median diameter of about 6 μm to about 15 μm or about 7 μm to about 14 μm as determined by laser diffraction.

4. The Intracameral Implant according to claim 1, wherein the travoprost particles have a median diameter of about 8 μm to about 13 μm as determined by laser diffraction.

5. The intracameral implant according to claim 1, wherein the travoprost particles have a median diameter of about 7 μm to about 10 μm or about 8 μm to about 9 μm as determined by laser diffraction.6* The intracameral implant according to claim 1, wherein the travoprost partlcies have a median diameter of about 8 μm or about 9 μm as determined by laser diffraction.

7. The intracameral implant according to claim 1, wherein the travoprost particles have a median diameter of about 9 μm to about 14 μm or about 10 μm to about 13 μm as determined by laser diffraction.

8. The intracameral implant according to claim 1, wherein the travoprost particles have a median diameter of about IQ μm or about 11 μm as determined by laser diffraction.

9. The intracameral implant according to claim 1, wherein the travoprost particles have a median diameter of about 12 μm or about 13 ym as determined by laser diffraction.

10. The intracamerai implantaccordingtoclaim 1.whereintheparticlesizedistributionofthetravoprost particlesasdeterminedbylaserdiffraction ischaracterizedasfallows: DIOofabout3pfntoabout9gm, D50ofabout7μmtoabout 14μm, and D9Gof uptoabout50μm,suchas D90ofabout12toabout26 ym.

11. Theintracamerai implantaccording tociaim 1,wherein theparticlesizedistributionofthetravoprost particlesasdetermined bylaserdiffraction ischaracterizedasfollows: D10ofabout5μm toabout9μm, D50ofabout9pffitoabout14μm, andD90ofabout 13μmtoabout26μm.

12. Theintracamerai implantaccording toclaim 1,whereintheparticlesizedistributionofthetravoprost particlesasdeterminedbylaserdiffraction ischaracterizedasfollows: DIOofabout6 μmtoabout8μm, D50ofabout10μmtoabout 13 μm, andD90ofabout 14μmtoabout25pin.

13. Theintracamerai implantaccording tociaim 1,wherein theparticlesizedistributionofthetravoprost particlesasdeterminedbylaserdiffractionischaracterized asfollows: DIOofabout3 μmtoabout6μm, D50ofabout7μmtoabout10μm,andD90ofabout 12μmtoabout16μm.

14. Theintracamerai implantaccording tociaim 1,wherein theparticlesizedistributionofthetravoprost particlesasdetermined bylaserdiffraction ischaracterizedasfollows: DIOofabout4μm toabout5μm, D50ofabout8μmtoabout9μm,and D90ofabout13μmtoabout15μm, 15. The intracamerai implantaccording toanyoneoftheprecedingclaims, whereinthetravoprostparticles compriseabout40wt-%toabout50wt-%orabout41 wt-%toabout49wt-%travoprostbasedonthe totalmassofthetravoprostparticles.

16. The Intracamerai Implantaccordingtoanyoneoftheprecedingclaims, whereinthetravoprostparticles compriseabout42wt-%toabout48wt-%orabout43 wt-%toabout47wt-%travoprostbasedonthe totalmassofthetravoprostparticles.

17. The Intracamerai implantaccordingtoanyoneoftheprecedingclaims, whereinthetravoprostparticles compriseabout42wt-%toabout44wt-%orabout45wt-%toabout47wt-%orabout46wt-%toabout 48wt-%travoprostbasedontoetotal massofthetravoprostparticles.

18. Theintracamerai implantaccordingtoanyoneoftheprecedingclaims, whereinthetravoprostparticles compriseabout40wt-%toabout47wt-%orabout41 wt-%toabout46wt-%travoprostbasedonthe totalmassofthetravoprostparticles, 19. Theintracamerai implantaccordingtoanyoneofthepreceding claims,whereinthetravoprostparticles compriseabout45wt-%toabout47wt-%orabout41wt-%toabout43wt-%orabout40wt-%toabout 42wt-%travoprostbasedonthetotal massofthetravoprostparticles.

20. The intracameral implant according to any one of the preceding claims, wherein the intracameral implant comprises only one type of travoprost particles.

21. The intracameral implant according to any one of the preceding claims, wherein the biodegradable polymer comprises or consists of a poiyiactide-co-glyco!ide or a polylactide, optionally wherein the biodegradable polymer comprises or consists of a polyiactide, such as a poiy(DL)lactlde.

22. The intracameral implant according to any one of the preceding claims, wherein 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.

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, optionally 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:-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, or-has an an inherent viscosity specification from about 0-4S di / g to about 0,88 d| / 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.

25. 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 dl / g to about 0,45 dl / g, as measured at 0.5% 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 the travoprost particles.27.. 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 4 gm to about 6 μm, D50 of about 8 μm to about 10 μm, and D90 of about 13 μm to about 15 μm,optionally wherein the partide size distribution of said travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 5 μm, D50 of about 9 μm, and D90 of about 14 μm.

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 foliows; DID of about 7 μm to about 9 μm, D50 of about 11 μm to about 13 μm, and D90 of about 14 μm to about 16 μm, optionally wherein the partide size distribution of said travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 8 μm, D50 of about 12 μm, and DOO of about 15 μm.

29. 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 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. The intracameral implant according to claim 29, 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 total mass of the travoprost particles, 31. The intracameral 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: D10 of about 4 μm to about 6 μm, D50 of about 7 μm to about 9 μm, and D9Q of about 12 μm to about 14 μm, optionally wherein the particle size distribution of said travoprost particles as determined by laser diffraction is characterized as follows: D10 of about 5 μm, D50 of about 8 μm, and D90 of about 13 μm.

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 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 di / g to about 1.00 dl / g, as measured at 0.S% 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 partide size distribution of said travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 3 μm to about 5 μm, D50 of about 7 μm to about 9 μm, and D90 of about 12 μm to about 14 μm, optionally wherein the particle size distribution of the travoprost: particles as determined by laser diffractionIs characterized as follows; DIG of about 4 μm, D50 of about 8 μm, and D9Q of about 13 μm36, The intracamera! 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 μm to about 7 μm, 050 of about 9 μm to about 11 μm, and D90 of about 13 μm to about 15 μm, optionaiiy wherein the particle size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 6 μm, D50 of about 10 μm, and D90 of about 14 μm.

37. 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 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.

38. The intracameral 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 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.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: Did of about 4 μm to about 6 μm, D50 of about 8 μm to about 10 μm, and D9G of about 14 μm to about 16 μm, optionally wherein the particle size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: D10 of about 5 μm, D50 of about 9 μm, and D90 of about 15 μm.

41. 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: D10 of about 5 μm to about 7 μm, D50 of about 12 μm to about 14 μm, and D90 of about 24 μm to about 26 μm, optionally wherein the partide size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: D10 Of about 6 gm, D50 of about 13 μm, and D90 of about 25 μm.

42. The intracameral implant according to any one of the preceding ciaims, wherein the 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 the 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 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.

47. The intracamerai 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 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.

49. The intracameral implant according to any one of the preceding claims, wherein the 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 about 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 intracamerai 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 22 wt-% to about 30 wt-% or about 24 wt-% to about 28 wt-% of travoprost54. The intracameral implant according to arty 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 μg to about 40 μg or about 15 μg to about 35 μg of travoprost.

56. The intracameral implant according to any one of the preceding claims, wherein the implant comprises a dose of about 20 μg to about 30 μg or about 25 μg to about 30 μg of travoprost.

57. The intracamerai implant according to any one of the preceding claims, wherein the implant comprises a dose of about 22 μg to about 30 μg or about 24 μg to about 28 μg of travoprost.

58. The intracameral implant according to any one of the preceding claims, wherein the implant comprises a dose of about 25 μg to about 27 μg or about 26 μg 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 intracamerai implant according to any one of the preceding claims, wherein the implant has a total weight of about 50 μg to about 150 pg, or of about 75 μg to about 125 μg 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 μg to about 120 μg or of about 90 μg to about 110 μg in its dried state.

62. The intracamerai implant according to any one of the preceding claims, wherein the implant has a total weight of about 95 μg to about 105 μg in its dried state.

63. The intracamerai implant according to any one of the preceding claims, wherein the implant has a total weight of about 100 μg in its dried state.

64. The intracamerai implant according to any one of the preceding claims, wherein the content of the biodegradable poiymer 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 intracamerai implant according to any one of the preceding claims, wherein the content of the biodegradable poiymer 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-%.

66. The intracamera! 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 29 μg to about 39 pg or about 31 pg to about 37 μg,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 μg to about 36 pg or about 33 pg to about 35 μg or ataut 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 intracameral implant according to ciaim 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 readout 0.18 mm or about 0.17 mm in its dried state.

72. The intracamera! 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 intracamera! 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 the 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 impiant comprises a dose of about 30 μg to about SO μg or about 35 μg to about 45 μg of travoprost.

76. The intracameral implant according to claim 75, wherein the impiant comprises a dose of about 36 pg to about 44 μg or about 37 μg to about 43 μg of travoprost.

77. The intracameral implant according to claim 76, wherein the implant comprises a dose Of about 38 pg to about 42 μg or about 39 μg to about 41 μg of travopro&t.

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 to 78, wherein the implant is in the 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 μg to about 400 pg, or of about 320 μg to about 380 pg in its dried state.

81. The intracameral implant according to claim S0fwherein the implant has a total weight of about 330 pg to about 370 μg or of about 340 μg to about 360 μg 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 μg 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 polymer with respect to the total weight of the Intracameral implant in Its dried state is about 10 wt-% io 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 its 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 biodegradable polymer in the implant in its dried state is about 47 μg to about 57 pg or about 49 pg to about 55 pg.

87. The Intracameral implant according to claim 86, wherein the total mass of the biodegradable polymer in the Implant in its dried state Is about 50 μg to about 54 μg or about 51 μg 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 intracamerai implant according to any one of the preceding claims, wherein the polymer network comprises one or more unite of polyethylene giycoi being cross-linked including a group represented by the foliowing 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,91. The intracameral implant according to any one of the preceding claims, wherein the polymer network comprises one or more unite of a multi-arm polyethylene glycol having 4 arms or S arms, such as 8 arms,92. The intracamerai: implant according to any one of the preceding claims, wherein the multi-arm polyethylene giycoi 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 15,000 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 glyco! precursor with a nucleophilic group-containing cross-linking agent.

94. The intracamerai implant according to ciaim 93, wherein the nucleophilic group is an amine.

95. The intracamerai implant according to claim 94, wherein the nucleophilic group-containing cross-linking agent has a molecular weight below 1,000 Da and comprises two or more primary aliphatic amine groups.

96. The intracamerai implant according to any one of claims 93 to 95, wherein the nucleophilic group- containing cross-linking agent is a diiysine, trilysine, tetraiysine, ethyienediamine, 1,3-diaminopropane, 1,3- dlaminopropane, diethyienetrlamine, or trimethylhexamethylenediamlne.

97. The intracamerai implant according to ciaim 96, wherein the nucteophiifc group-containing cross-linking agent is a trilysine, such as a salt of trilysine, such as trilysine acetate.

98. The intracameral implantaccordingtoanyoneofclaims93to97,whereintheelectrophilicgroupis succinimidyiglutarate(SG),succinimidyisuccinate(SS),succinimidyicarbonate(SC),succinimidyiadipate (SAP), and / orsuccinimidyiazelate(SAZ).

99. Theintracameral implantaccordingtoclaim98,whereintheelectrophilicgroupissuccinimidyiazelate (SAZ). 100.The intracameral implantaccording toanyoneofclaims93to99,whereinthepolyethyleneglycol precursorhasfrom2to 10armsorfrom4to8arms. 101.The intracameral implantaccordingtoanyoneofciaims93to 100, whereintoepolyethyleneglyco! precursorhas4armsor8arms, suchas8arms. 102.The intracameral implantaccordingtoanyoneof claims93to101, whereinthemulti-armpolyethylene glyco!inthemulti-armpolyethylenegiycol precursorhasan averagemolecularweightfromabout10,000 Datoabout20,000Daorfromabout12,500Datoabout17,500Da,such asabout15,000Da, 103.The Intracameral implantaccordingtoanyoneofclaims93to102, whereintheelectrophilicgroup- containingmulti-armpolyethyleneglycolprecursoris8-arm-15K-PEG-SAZ. 104.The intracameral implantaccording toanyoneofclaims93 to103, wherein toeweightratioofthe electrophilicgraup-containingmulti-armpolyethyleneglyco! precursortothenucleophilicgraup-containing cross-linkingagentisfromabout14:1toabout 18:1, orfromabout15:1toabout 17:1,orabout 16:

1. 105.The intracameral implantaccordingtoanyoneoftheprecedingclaims, whereinthecontentofthe biodegradablehydrogelwithrespecttothetotalweightoftheintracameralimplantin itsdriedstateis about30wt-%toabout50wt-%orabout34wt-%toabout42Wt-%, 106.Theintracameral implantaccording toanyoneoftheprecedingclaims,whereinthecontentofthe biodegradablehydrogelwithrespecttothetotalweightoftheintracameralimplant:initsdried stateis about35wt-%toabout45wt-%orabout36wt-%toabout40wt-%, 107.The intracameralimplantaccording toanyoneoftheprecedingclaims,whereinthecontentofthe biodegradablehydrogelwithrespecttothetotalweightoftheintracameralimplantin itsdried stateis about37wt-%toabout39wt-%orabout38wt-%. lOS.The intracameral implantaccording toanyoneoftheprecedingclaims,whereinthetotalmassoftoe biodegradablehydrogelintheintracameral implantinitsdriedstateisabout30pgtoaboutSOpgorabout 34μgtoabout42μg.

109. The intracameral implant according to arty orte 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 μg to about 40 pg.UQ.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 hydrogel with respect to the total weight of the intracameral implant in its dried state is about 60 wt-% to about SO wtor about 65 wt -% to about 75 wt-%.112,The intracameral implant according to ciaim ill, wherein the content of the biodegradable hydrogel with respect to the totai weight of the intracamera! 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 ciaim 112, wherein the content of the biodegradable hydrogel with respect to the total weight of the intracamera! implant iri its dried state is about 69 wt-% to about 71 wt-% or about 70 wt-%.114,'The intracameral 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 μg to about 255 pg.115,The intracameral implant according to ciaim 114, wherein the total mass of the biodegradable hydrogel in the intracameral implant in its dried state is about 240 μg to about 250 μg or about 242 pg to about 248 pg-116. The intracameral implant according to claim 115, wherein the totai mass of the biodegradable hydrogel in the intracameral implant in its dried state is about 244 μg to about 246 μg or about 245 pg. llZ.The intracameral implant according to any one of the preceding claims, wherein the implant shows a travoprost / 7? 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 in 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 / / ? vitro release of about 10% to about 25% or about 10% to about 20% based on the totalweight of toavoprost in the intraeameral Implant after incubating the intraeameral implant for 1 day 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,119>The intraeameral implant according to any one of the preceding claims, wherein the implant shows a travoprost in vitro release of less than about 50% or less than about 40% or less than about 30% based on the total weight of travoprost in toe intraeameral implant after incubating the intraeameral implant tor 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.

120. The intraeameral implant according to any one of the preceding claims, wherein the implant: shows a travoprost in vitro release of less than about 80% or less than about 70% or less than about 80% based on the total weight of travoprost in the intraeameral implant after incubating the intraeameral implant tor 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 intraeameral implant according to any one of the preceding claims, wherein 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 tn the intraeameral implant after incubating the intraeameral 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,122. The intraeameral 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 total weight of travoprost in the intraeameral implant after incubating the intraeameral 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 intraeameral 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 total weight of travoprost in the intraeameral implant after incubating the intraeameral implant for 100 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 37aC,124.The intraeameral implant according to any one of the preceding claims, wherein the implant shows an essentially zero-order travoprost .w wfro release profile when incubating the Intraeameral 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 intraeameral 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.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 intracamerai implant for about 0.5 months or longer, or about 1 month or longer, or about 1.5 months or Icsnger, 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 intracamerai implant according to any one of the preceding ciaims and an injection device for intracamerai injection of the intracamerai implant, optionally wherein the injection device is a syringe and / or wherein the injection device is loaded with the intracamerai implant.

127. A syringe for intracamerai injection,, wherein the syringe is loaded with an intracamerai implant according to any one of claims 1 to 125.

128. Travop rest 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 μm to about 19 μm as determined by laser diffraction.

129. The travoprost particles according to claim 128, wherein the travoprost particles have a median diameter of about 4 μm to about 17 μm or about 5 μm to about 16 μm as determined by laser diffraction.

130. The travoprost particles according to claim 128, wherein the travoprost particles have a median diameter of about 6 μm to about 15 μm or about 7 μm to about 14 μm as determined by laser diffraction,131. The travoprost particles according to claim 128, wherein the travoprost particles have a median diameter of about 8 μm to about 13 μm as determined by laser diffraction132.The travoprost particles according to claim 128, wherein the travoprost particles have a median diameter of about 7 μm to about 10 μm or about 8 μm to about 9 μm as determined by iaser diffraction.133.The travoprost particles according to claim 128, wherein the travoprost partides have a median diameter of about 8 μm or about 9 μm as determined by iaser diffraction.134.The travoprost particles according to claim 128, wherein the travoprost particles have a median diameter of about 9 μm to about 14 μm or about 10 μm to about 13 μm as determined by laser diffraction.135, The travoprost particles according to claim 128, wherein the travoprost particles have a median diameter of about 10 μm or about 11 μm as determined by laser diffraction.136.The travoprost particles according to claim 128, wherein the travoprost particles have a median diameter of about 12 μm or about 13 μm as determined by laser diffraction.137.The travoprost particles according to ciaim 128, wherein the particle size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 3 μm to about 9 gm, D50 of about 7 μm to about 14 μm, and D9G of up to about 50 μm, such as D90 of about 12 to about 26 μm.

138. the travoprost particles according to claim 128, wherein the particie size distribution of the travoprost particles as determined by laser diffraction Is characterized as foltows: DIO of about 5 μm to about 9 μm, D50 of about 9 μm to about 14 μm, and D90 of about 13 μm to about 26 μm. 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 follows: DIG of about 6 μm to about 8 μm, D58 of about 10 μm to about 13 μm, and D90 of about 14 μm to about 25 μm.

140. The travoprost partides 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 3 μm to about 6 μm,D50 of about 7 μm to about 10 μm, and D90 of about 12 μm to about 16 μm.

141. 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: DIG of about 4 μm to about 5 μm, D50 of about 8 μm to about 9 μm, and DOO of about 13 μm to about 15 μm.142, The travoprost particles according to any one of claims 138 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 vrt-% to about 47 wt-% travoprost based on the total 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 tota! mass of the travoprost particles.145, The travoprost particles according to any one of 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,146,The travoprost particles according to any one of claims 128 to 145, wherein toe 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 particles147,The travoprost particles according to any one of claims 128 to 146, wherein toe biodegradable polymer comprises or consists of a polylactide-co- glycolide or a polylactide.148, The travoprost particles according to any one of claims 128 to 147, wherein toe biodegradable polymer comprises or consists of a polylactide, such as a poiy(DL)iactide,149.The travoprost partides according to any one cf claims 128 to 148, wherein the biodegradable, polymer comprises or consists of a polylactide and wherein the polylactide has an acid end group, csptionally wherein the polylactide is a poly{DL)lactide.15G,The travoprost partides according to any one of claims 128 to 149, wherein toe biodegradable polymer comprises or consists of a polylactide and wherein the polylactide has an ester end group, optionally wherein the polylactide is a poly(OL)factide,151. The travoprost particles according to any one of claims 128 to 150, wherein said travoprost particles are a mixture of travoprost and a biodegradabie polymer consisting of a polylactide, wherein said polylactide:-has an inherent viscosity specification from about 0,50 di / 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, 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 / y in chloroform at 25°C, and optionally has an ester end group.152.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 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,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 toe travoprost particles,154. The travoprost particles according to daim 152 dr 153, wherein the partide size distribution of said travoprost partides as determined by taser diffraction is characterized as follows: DIO of about 4 μm to about 6 μm, D50 of about 8 μm to about 10 gm, and D90 of about 13 μm to about 15 μm, optionally wherein the partide size distribution of said travoprost partides as determined by laser diffraction is characterfeed as foiiows: DIO of about 5 ym, D50 of about 9 ym, and D90 of about 14 μm.1.55.The travoprost particles according to claim 1S2 or 153, wherein the particle size distribution of said travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 7 ym to about 9 μm, D50 of about 11 μm to about 13 μm, and D90 of about 14 μm to about 16 μm, optionally wherein the particle size distribution of said travoprost particles as determined by laser diffraction is characterized as follows: DIO of about 8 μm, D50 of about 12 μm, and D90 of about 15 gm.

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 polyiactide having an add 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 3Q°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 total mass of the travoprost particles,158. The travoprost partides according to claim 156 or 157, wherein the partide size distribution of said travoprost particles as determined by laser diffraction is characterized as follows: D10 of about 4 μm to about 6 μm, D50 of about 7 gm to about 9 μm, and D90 of about 12 μm to about 14 gm, optionally wherein the particle size distribution of said travoprost particles as determined by laser diffraction is characterized as follows; D10 of about 5 μm, D50 of about 8 μm, and D90 of about 13 μm.

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 polyiactide having an add 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%.

160. Th e travoprost particles according to ciaim 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 total mass of the traveprcsst particles.161,The travoprost partides according to claim 159, wherein said travoprost partides 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 toe travoprost partides, 162, The travoprost partides according to any one of claims 159 to 161, wherein toe particle size distribution of said travoprost particles as determined by laser diffraction is characterized as follows: D10 of about 3 μm to about 5 μm, D50 of about 7 μm to about 9 μm, anti D90 of about 12 μm to about 14 μm, optionally wherein the partide size distribution of the travoprost partides as determined by laser diffraction is characterized as foltows: DIO of about 4 μm, D50 of about 8 μm, and D90 of about 13 μm.

163. The travoprost particles according to any one of claims 159 to 161, wherein toe particle size distribution of said travoprost partides as determined by laser diffraction is characterized as follows: DIO of about 8 μm to about 7 μm, D50 of about 9 μm to about 11 μm, and D90 of about 13 μm to about 15 μm, optionally wherein the partide size distribution of the travoprost particles as deterirtined by laser diffraction is characterized as follows: DIO of about 6 μm, 050 of about 10 μm, and D9Q of about 14 μm.164.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 polyiactide 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.165.The travoprost particles according to claim 164, 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 toe 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 c;f the travoprost particles,167.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 4 μm to about 6 μm, 050 of about 8 μm to about 10 μm, and D90 of about 14 μm to about 16 μm, optionally wherein toe particle size distribution of the travoprost particles as determined by laser diffraction is characterized as follows: DID of about 5 μm, 050 of about 9 μm, and D90 of about 15 μm. 168.The travoprost particles according to any one of claims 164 to 166, wherein the particle size distribution of said travoprost partides as determined by laser diffraction is characterized as follows: D10 of about 5 μm to about 7 μm, DS0 of about 12 μm to about 14 μm, and D90 of about 24 μm to about 26 μm,optfonally wherein the partide size distribution of the travoprost particles as determined by laser diffraction is characterized as fellows: DIO of about 6 μm, D50 of about 13 μm, and DOO of about 25 μm.169.The travoprost particles according to any one of ciaims 128 to 188, wherein the travoprost particles are obtained by or are obtainable by a process comprising a membrane emulsification step.170,The travoprost particles according to 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 μm to about 7.5 μm, such as about 5 μm.171, The travoprost particles according to any one of claims 128 to 169, wherein the travoprost particles are obtained by or are obtainable toy 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 soludon 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 μm to about 7.5 μm, such as about 5 μm, and-hardening the travoprost particles.172,The travoprost particles according to any one of claims 128 to 169, wherein toe 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 μm to about 7.5 μm, such as about 5 μm,-hardening the travoprost particles, and -purifying the hardened travoprost particles.173, The travoprost particles according to any one cf claims 128 to 169, wherein toe travoprost particles are obtained by or are obtainable by a process composing;-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 μm to about 7.5 μm, such as about 5 μm,-hardening the travoprost particles,‘purifying the travoprost particles, and-drying the travoprost particles.174.The travoprost particles according to any one of ciaims 178 to 173, wherein toe first solution is an organic solution of travoprost and toe biodegradable polymer, optionally wherein the organic solvent is dichloromethane and / or optionally 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 toe 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 the concentration of travoprost in toe 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 178 to 174, wherein toe 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% w / w, polyvinyl alcohol.176.The travoprost particles according to any one of claims 171 to 175, wherein toe first solution is an organic solution of travoprost: and toe biodegradable polymer and wherein the organic solvent is evaporated and extracted during hardening the travoprost particles, optionally wherein the organic solvent is dtchiorometoane.177, The 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 for at least about 16 hours or from about 18 hours to about 24 hours, optionally wherein hardening is carried out under stirring and / or a nitrogen sweep.178,The travoprost particles according to any one of claims 172 to 177, wherein toe 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 fiitration, further csptionally wherein purifying the hardened travoprost particles concomitantly concentrates the hardened travoprost particles.179.The travoprost particles according to any one of claims 173 to 178, wherein drying the travoprost partides comprises or consists of lyophilizing the travoprost particles.180 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.181.A method of manufacturing travoprost particles, wherein the travoprost particles are a mixture of travoprost and a biodegradable polymer and wherein the method comprises:-pravidlng or preparing a first: solution comprising travcsprost 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 μm to about 7.5 μm, such as about 5 μm.182, 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,-passing the first solution through a membrane with pores into the second soiubon to provide the travoprost particles, optionally wherein the membrane pore size is from about 2.5 μm to about 7.5 μm, such as about 5 μm, and-hardening the travoprost particles.1.

83. 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, -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 μm to about 7.5 μm, such as about 5 |j:m,-hardening the travoprost particles, and-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 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, -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 μm to about 7.5 μm, such as about 5 μm,"hardening the travoprost particles, -purifying the travoprost particles, and•frying the travoprost particles. 135, The method of any one of claims 181 to 184. wherein the first solution is an organic solution of travoprost and the biodegradable polymer, optionally wherein the organic solvent is dichtaromethane and / or optionally 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 the concentration of travoprost in the first solution is from about 48 % to about 65% w / v, such as about 50% w / v. 186.1 he method of any one of claims 181 to 185, wherein the second solution is an aqueous solution of polyvinyl alcohol, optionally of about (1.5% w / w to about 1.5% w / w, such as about 1% w / w, polyvinyl alcohol187, The method of any one of claims 182 to 186, 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 dichiorometbane.188,The method of any one of claims 182 to 187, wherein hardening the travoprost partides is conducted for at (east about 12 hours or for at least about 16 hours or from about 18 hours to about 24 hours, optionally 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 hardened travoprost particles concomitantly concentrates the hardened travoprost particles.

190. The method of any one of claims 184 to 189, wherein drying the travoprost particles comprises or consists of lyophilizing the travoprost particles. iSl.The method of any one of claims 180 to 190, wherein the biodegradable polymer is defined as tn any one of claims 128 to 168 or wherein the travoprost particles are defined as in any one of claims 128 to 168.192.Travuprost: particles obtainable by or obtained by the method according to any one of claims 180 to 191.193.A method of manufacturing a travoprost sustained release biodegradable intracameral implant, the method comprising:-preparing or providing travoprost particles according to 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 travaprost particies,-crosslinking the precursor mixture using a nucleophilic group-contetnlng crosslinking agent to form a polymer 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.

194. A method of manufacturing a travoprost sustained release biodegradable intracameral implant, the method comprising:-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, -crosslinking the precursor mixture using a nucleophilic group-containing crossiinking agent to form a polymer network, thereby obtaining a biodegradable hydrogei comprising the polymer network, wherein the travoprost particies are dispersed in the biodegradabie hydrogei, and -drying the biodegradable hydrogel to provide the implant. IQS.The method of claim 193 or 194, wherein the electrophilic group-containing mufti-arm polyethylene glyco! precursor and / or the nucleophilic group-containing crosslinking agent are defined as in any one of claims 94 to 104.196.A travoprost sustained release biodegradable intracameral implant obtainable by or obtained by the method of any one of ciaims 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: In need of treatment, 198. A method of treating glaucoma 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.

199. A method of reducing the intraocular pressure in a subject with glaucoma comprising inserting an Intracameral Impiant according to any one of claims 1 to 125 and 196 into an eye of the subject in need of treatment200. The method of claim 198 ar 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 intracamera! implant according to any one of claims 1 to 125 and 196 into an eye of the subject in need of treatment202.A method of reducing the intraocular pressure in a subject with ocular hypertension comprising inserting an intracameral implant according to any one of daims 1 to 125 and 196 into an eye of the subject in need of treatment.

203. 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.204.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 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.207.The method of any one of claims 197 to 206, wherein 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, optionally wherein the new intracameral implant is an intracameral implant according to any one of daims1 to 125 and 196, and further optionally wherein the new Intracameral Implant is the same as the 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 sustained release of travOprost into the aqueous humor.210.The method of any one of claims 1.97 to 209, wherein the subject is a human.211.The intracameral implant according to any one of claims 1 to 125 and 196 for use as a medicament.212.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 a medicament.214, Use of the Intracamerai implant according to any one of claims 1 to 125 and 196 in the manufacture of a medicament tor a method of any one of claims 197 to 210,215,A method of treating an ocular disease 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 treatment,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 treatment.

217. A method of reducing the intraocular pressure in a subject with glaucoma comprising administering the travoprost particles according to any one of ciaims 128 to 179 and 192 into an eye of the subject in need of treatment.218.The method of claim 216 or 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 travoprost particles according to any one of claims 128 to 179 and 192 into an eye of the subject in need of 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 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 medicament.

223. Use of the travoprost partides according to any one of claims 128 to 179 and 192 in the manufacture of a travoprost sustained release biodegradable intracameral implant.224, Use of the travoprost particles according to any one of claims 128 to 179 and 192 in the manufacture of a medicament tor a method of any one of claims 215 to 221.

225. The travoprost particles according to any one cf claims 128 to 179 and 192 for use as a medicament.

226. The travoprost particles according to any one of claims 128 to 179 and 1.92 tor use in a method of any one of claims 215 to 221.

Images