Drug development ophthalmic formulations

The class II methods involve the calculation of a quantity of water needed to make an isotonic solution for a given amount of drug, followed by dilution with an isotonic solution to make up the volume. These methods were developed to enable pharmacists to prepare parenteral and ophthalmic formulations with simplicity and ease. 

Stablizers. Stabilizers are ingredients added to a formula to decrease the rate of decomposition of the active ingredients. Antioxidants are the principal stabilizers added to some ophthalmic solutions, primarily those containing epinephrine and other oxidizable drugs. Sodium bisulfite or metabisulfite are used in concentration up to 0.3% in epinephrine hydrochloride and bitartrate solutions. Epinephrine borate solutions have a pH range of 5.5 7.5 and offer a more difficult challenge to formulators who seek to prevent oxidation. Several patented antioxidant systems have been developed specifically for this compound. These consist of ascorbic acid and acetylcysteine, and sodium bisulfite and 8-hydroxyquinoline. Isoascorbic acid is also an effective antioxidant for this drug. Sodium thiosulfate is used with sodium sulfacetamide solutions. 

The final example of a novel process development formulation involves a semi-solid ophthalmic gel containing a carbonic anhydrase inhibitor drug for the treatment of glaucoma. It is administered to the patient by extruding the gel from an ophthalmic tube into the conjunctival sac of the eye. The drug had a very low aqueous solubility. It was necessary to reduce the particle size of the drug to less than 10 pim and suspend it in a very thick carbomer gel vehicle, to increase the residence time of the gel and maximise corneal permeation. The formulation details are given below ... 

Inactive ingredients are incorporated into the formulation, which prevent oxidation or reduction of the drug substance in solution. Salts are added to make the solution isotonic and the pH is adjusted to most closely assimilate physiologic pH. These concerns are particularly important in the development of ophthalmic solutions. 

Other biomedical applications of polymers include sustained and controlled drug delivery formulations for implantation, transdermal and trans-cornealuses, intrauterine devices, etc. (6, 7). Major developments have been reported recently on the use of biomaterials for skin replacement (8), reconstruction of vocal cords (9), ophthalmic applications such as therapeutic contact lenses, artificial corneas, intraocular lenses, and vitreous implants (10), craniofacial, maxillofacial, and related replacements in reconstructive surgery (I), and neurostimulating and other electrical-stimulating electrodes (I). Orthopedic applications include artificial tendons (II), prostheses, long bone repair, and articular cartilage replacement (I). Finally, dental materials and implants (12,13) are also often considered as biomaterials. 

As excipients, CDs have been widely used to cover the bitter taste of drugs, to increase their dissolution rates, to reduce irritation reactions and in low concentrations to suppress the haemolysis induced by some drugs [180]. Great effort has been made to develop CD-based drug formulations with different administrative routes, including parenteral, oral, pulmonary, nasal [181], transdermal, rectal [182] and ophthalmic [183] drug delivery [184]. 

Ophthalmic diseases are most commonly treated by topical instillation of eye drops. These formulations evidence limitations like poor stability and efficacy, reduced cor-neal/scleral permeability, systemic toxicity and lack of compUance [2]. In this sense, the development of effective therapies for visual disorders is of high priority [1], which makes the field of ocular delivery one of the most interesting and challenging areas for pharmaceutical scientists [3]. There has been significant research directed towards the development of new systems for controlled drug delivery in ophthalmology such... 

The principal route for local ophthalmic drug delivery remains topical application [15], justified by the ease of application and patient compliance [16], cost advantage, and simplicity of formulation development and production [16]. This route of administration represents nearly 90% of the marketed formulations. 

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