Sustained-release oral dosage forms

When absorption takes place rapidly, which is usual for conventional dosage forms, fca > kd, but when absorption takes place slowly and ka < k(j the flip-flop phenomenon occurs, whereby the rate of absorption controls the rate of elimination of the drug. This situation applies not only to sustained-release oral dosage forms administered to dogs, but also to phenylbutazone and meclofe-namic acid in horses, salicylate administered as an aspirin bolus to cattle and oral suspensions of benzimidazole anthelmintics in ruminant species. 

There are approximately a dozen calcium channel antagonists marketed in the United States for the treatment of hypertension, certain dysrhythmias, and some forms of angina (see Chaps. 13,15, and 17). The calcium channel blockers are classified by their chemical structure as phenylalkylamines (e.g., verapamil), benzothiapines (e.g., diltiazem), and dihydropyridines (e.g., amlodipine, felodipine, nicardipine, and nifedipine). Several of these agents, namely, diltiazem, nicardipine, nifedipine, and verapamil, are formulated as sustained-release oral dosage forms or have a slow onset of action and longer half-life (e.g., amlodipine " ), allowing once-daily administration. 

Hilton, A. K., and Deasy, P. B. In vitro and in vivo evaluation of an oral sustained-release floating dosage form of amoxycillin trihydrate. Int. J. Pharm. 86 79-88, 1992. 

Thus polymers serve as key excipients in oral and parenteral CR formulations. Other excipients used in sustained release dosage forms have been covered in other chapters within this book. For example, parenteral CR dosage forms involving polymers would still have other excipients as discussed in the chapter on injectable excipients (Chapter 16). Similarly oral dosage forms will require consideration of other excipients depending on the nature of the drug, as discussed in Chapter 12. This chapter reviews some of the promising polymers used in this application. 

Dosages and routes of administration Dihydrocodeine is mostly used in the form of immediate or sustained release oral formulations (Lloyd et al., 1992). For pain treatment the dose range is 30-80 mg, for cough inhibition doses are in the range of 10 mg. 

FIGURE 22.1 Atypical plasma concentration pro le comparing differences between immediate-release (IR), sustained-release (SR), and controlled-release (CR) oral dosage forms. 

In human medicine, the majority of drugs are formulated as oral dosage forms. Concerns of user non-compliance have led to the development of sustained release formulations. While user noncompliance is also a concern in veterinary medicine, the focus is on the pet owner administering the drug. 

Mannitol has also been used to prevent thickening in aqueous antacid suspensions of aluminum hydroxide (<7% w/v). It has been suggested as a plasticizer in soft-gelatin capsules, as a component of sustained-release tablet formula-tions, and as a carrier in dry powder inhalers. It is also used as a diluent in rapidly dispersing oral dosage forms. 

White wax is also used as a film coating in sustained-release tablets. White beeswax microspheres may be used in oral dosage forms to retard the absorption of an active ingredient from the stomach, allowing the majority of absorption to occur in the intestinal tract. Wax coatings can also be used to affect the release of drug from ion-exchange resin beads. 

B. Oral. A large number of oral dosage forms are available formulated in both immediate and sustained-release formulations. 

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