Prolonging or Extending Drug Release

Sustaining drug release may be best affected using resins with strong exchange propensity, high cross linkage and having larger particle size. Reduced load of API is


Fig. 8.6 Release profile of dextromethorphan (DM) from Delsym® 12-Hour [18]


Fig. 8.6 Release profile of dextromethorphan (DM) from Delsym® 12-Hour [18]

also beneficial. Release can also be sustained or delayed by coating the resinate particles with a semipermeable membrane, providing a rate limiting barrier to diffusion to the surrounding medium. Membrane structure and thickness can be designed to complement the release properties of the resinate and synchronize delivery with therapeutic requirements. The nature of release-controlling polymers and their properties such as permeability and pH sensitivity are discussed elsewhere in this book.

An immediate-release drug layer can also be applied on top of a controlled-release membrane, or a combination of immediate-release and controlled-release particles can be included in the dose unit, as happens with other controlled-release techniques. This can provide early plasma levels (and associated onset of action) while the slow release from the coated resin prolongs the therapeutic effect with certain drugs. Release profiles from a formulation of the antitussive agent, dextromethorphan hydrobromide, comprising a mixture of immediate-release and controlled-release particles to provide 12-h cover are shown in Fig. 8.6.

Resinates usually swell on hydration and such expansion can crack a controlled-release membrane, destroying its release-modifying properties. The Pennwalt Corporation developed a process to inhibit such fracture by pretreating resinate with an impregnating agent to keep resinate hydrated and swollen during coating [19]. Glycerin and polyethylene glycol are suitable impregnating agents, as are propylene glycol, mannitol, lactose and methylcellulose [20]. Such treatment did not affect drug release [21]. However, the possibility that residual moisture acquired during coating might destabilize moisture-sensitive drugs needs to be borne in mind.

8.6 Pharmaceutical Applications

In addition to modifying a drug's dissolution and release resinates have other unique features that could contribute to optimal dosage form design. Features include:

• Their insolubility and nonabsorbable nature renders resins safe for ingestion

• Masking of bitter tasting or irritant drugs

• Enhance chemical stability of a labile drugs

These features are exemplified in the following examples.

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