Azithromycin ophthalmic in-situ gel and preparation method thereof

Abstract

The invention discloses azithromycin ophthalmic in-situ gel. The azithromycin ophthalmic in-situ gel comprises the following components in percentage by weight: 0.1 to 5 percent of azithromycin, 0.05to 5 percent of cationic polysaccharide, 0.05 to 5 percent of sodium alga acid, 10 to 30 percent of poloxamer 407, 0.1 to 15 percent of poloxamer 188, 0.05 to 5 percent of cosolvent and buffer salt thereof, 0.01 to 5 percent of a tackifier, 0.01 to 5 percent of an antioxidant, 0.1 to 10 percent of an osmotic pressure regulator and 0.001 to 2 percent of a preservative. The prepared azithromycin ophthalmic in-situ gel still has proper solution-gel phase conversion ability when being used and diluted by tear, has excellent mucous membrane permeability and biological adhesive force, overcomes thedefects in the prior art, increases the ocular bioavailability of the medicine, improves corneal permeability, reduces eye irritant irritation and improves compliance of patients. The invention also discloses a preparation method of the gel, wherein the process is simple.

Description

technical field [0001] The invention relates to the field of ophthalmic drugs, in particular to an ophthalmic gel. Background technique [0002] Bacterial conjunctivitis is the most common infection. It is widely spread among different countries, races, ages and genders. It is easy to infect in densely populated areas such as kindergartens and schools. Although it has self-healing properties, it is resistant to infection Treatment can shorten the course of the disease, prevent infection, and reduce complications. Gram-positive Staphylococci, Streptococcus pneumoniae, and Haemophilus influenzae were the most common pathogens. Acute bacterial conjunctivitis is a highly contagious acute conjunctival inflammation that occurs mainly in summer and autumn and uses bacteria as the pathogen. It is the most frequently encountered eye disease in daily ophthalmology first visits. Bacterial keratitis and conjunctivitis often cause varying degrees of damage to eye tissues, sometimes wit...

AI Technical Summary

Problems solved by technology

[0006] In the ophthalmic drug delivery system, the traditional ophthalmic drug delivery form - eye drops, its principle of action is that the drug will be delivered with the secretion of tears after dripping into the ocular surface, which has the advantage of uniform drug distribution, but because the tear fluid in the conjunctival sac is not Stopped secretion and rapid elimination from the nasolacrimal duct, there are problems such as short residence time and low bioavailability, which are related to the very effective protection mechanisms of the eyes such as tearing and blinking reflex, so that the medicine dripped into the eye can quickly pass from the cornea The anterior area is eliminated, the contact time with the cornea is only about 1-2 minutes, and the bioavailability of the eye is generally less than 10%

In addition, a large amount of drugs enter the nasal cavity or digestive tract through the nasolacrimal duct and are finally absorbed systemically, which increases the risk of side effects and toxicity

Another traditional ophthalmic dosage form - eye ointment, which is usually made of petroleum jelly as a base, although it can provide a longer drug residence time, but it has a strong greasy feeling, which can cause blurred vision and eyelid crusting after use problems, and usually only at bedtime

The ophthalmic gel is a carrier with a hydrophilic polymer, which has good biocompatibility. It is in a semi-solid state, which can prolong the action time of the drug and reduce the number of medications. Difficult to control, lack of good spreadability

CN101103992A and CN1410071A each disclose a kind of preparation method of azithromycin eye drops, they use hyaluronic acid or other water-soluble macromolecule material as thickener, although improved the residence time of preparation in eye, but because dropability is not good but bad for dosing

Patent CN101444477A reports that poloxamer 407 and poloxamer 188 are used as temperature-sensitive substrates to prepare azithromycin eye drops, which can adjust the defect that the gelation temperature of poloxamer 407 alone is too low; in addition, patent CN104055729A discloses a Azithromycin ophthalmic gel, using both ion-sensitive and temperature-sensitive gel bases, has dual gelling properties. The ion-sensitive gel base is preferentially deacetylated gellan gum, and the temperature-sensitive gel base is preferentially poloxamer 407, which can reduce loss. , to overcome the problem of low gelation temperature when simply using poloxamer 407; but the shortcomings of the two patents are relatively low gelation strength and fast dissolution

There is a document "Research on Azithromycin Ophthalmic Immediate Gel" that uses Poloxamer 407 as the main matrix, together with an appropriate amount of polycarbophil, to increase bioadhesion, but polycarbophil molecules contain more The carboxyl group should not be neutralized by tears and cause eye irritation

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