Influence of formulation

The results of incorporating pilocarpine (V) (a relatively water-soluble dmg) and fluoro-metholone (a lipophilic dmg) into a water-inoil ointment base can be compared in Fig. 9.36. Pilocarpine is thought to be released only when in contact with aqueous tear fluid, whereas the steroid, being soluble in the base, can diffuse through the base to replenish the surface concentrations and thus produce a sustained effect. 

Hydrophilic polymeric vehicles, such as poly (vinyl alcohol) (PVA) and hydroxypropyl-methylcellulose (HPMC), are used in ophthalmic formulations. PVA increases the effectiveness of the dmg substance. HPMC has likewise been found to reduce the effective dose of neomycin sulfate required to prevent infection of corneas of experimental animals (Table 9.11). 

Eye drops are often formulated to be isotonic with tear fluid but deviations from tonicity do not cause problems, although hypertonicity may cause stinging of the eye and hypotonicity may increase the permeability of the cornea. 

Some ingredients of eye medications may increase the permeability of the cornea. Surface-active agents are knovm to interact with membranes to increase the permeability benzalkonium chloride has surfactant properties and may well have some effect on comeal permeability, although its primary purpose is as a bacteriostat and bactericide. Chlorhexidine acetate and cetrimide, both of which are surface-active, are also used. 

The influence of log P of beta-blockers (Table 9.12) on their permeation coefficients into conjunctiva and cornea is shown in Fig. 9.37. In humans, the conjunctiva has 17 times the surface area of the cornea and therefore it absorbs significant amounts of dmg. Work has centred on increasing corneal permeability or retention of the dmg (or product) in the conjunctiva sac. Appropriate doses of dmg can achieve a degree of comeal or conjunctival selectivity, represented in Fig. 9.37(c) by the ratio (C/y). Increasing lipophilicity increases the C// ratio from 0.1 to approximately 0.5. 

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C. Influence of Formulation and Processing Factors on Physical State of the Drug... 

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In this chapter, various aspects of drug photoreactivity are presented. Common photochemical reactions by which drugs have been found to decompose are described. The influence of formulation factors, e.g., excipients, on product stability is discussed. Finally, variables that have to be considered in photostability studies are noted. 

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