Modified Release Dosage Forms

Modified Release Dosage Forms

            Modified-release dosage forms (MRDF) have always been more effective therapeutic alternative to conventional or immediate-release dosage forms. The objective of MRDF for oral administration is to control the release of the therapeutic agent and thus control drug absorption from gastrointestinal tract. Such a dosage form effectively reduces adverse-effects associatedwith peak plasma concentration beyond that needed for therapeutic effectivenesswhilemaintaining the plasmalevel above or at that needed to achieve therapeutic effect for a longer period. The dosage form, in effect, controls the amount of drug available for absorption fromone dose administration to the next resulting in a morestable plasma level profile. By reducing the side-effect profile of drug entities and allowing for less frequent dosing regimens, these dosage forms may improve the overall cost-effectiveness of drug therapy. Therefore, MRDF for new chemical entities are being considered on a routine basis than ever before. Within the context of this discussion, the term modified-release refers to both delayed- and extended- or prolonged-release system for oral administration.

            Modified-release preparations can be administered orally in single or multiple-unit dosage forms. Single-unit formulations contain the active ingredient within the single tablet or capsule, whereas multiple-unit dosage forms comprise of number of discrete particles that are combined into one dosage unit. They may exist as pellets, granules, sugar seeds (non-pareil), minitablets, ion-exchange resin particles, powders, and crystals, with drugs being entrapped in or layered around cores. Although, similar drug release profiles can be obtained with both the dosage forms, multiple-unit dosage forms offer several advantages over single-unit systems such as nondisintegrating tablets or capsules. When multiple-unit systems are taken orally, the subunits of multiple-unit preparations distribute readily over a large surface area in the gastrointestinal tract and these small particles (b2 mm) behave like liquids leaving the stomach within a short period of time. Their small size also enables them to be well distributed along the gastrointestinal tract that could improve the bioavailability, which potentially could result in a reduction in local drug concentration, risk of toxicity, and side-effects. Interand intra-individual variations in bioavailability caused by, for example food effects, are reduced. Premature drug release from enteric-coated dosage forms in the stomach, potentially resulting in degradation of drug or irritation of gastric mucosa, can be reduced with coated pellets because of more rapid transit time when compared to enteric-coated tablets. In the multiple-unit system, the total drug is divided into many units. Failure of few units may not be as consequential as failure of a single-unit system. This is apparent in sustained-release single-unit dosage form, where a failure may lead to dose-dumping of the drug. Other advantages of this divided dose include ease of adjustment of the strength of a dosage unit, administration of incompatible drugs in a single dosage unit by separating them in different multiparticulates and combination of multiparticulates with different drug-release rates to obtain the desired overall release profile.