Investigation of the in vitro similarity of Pharmaceutical oral dosage forms using Dissolution testing as a surrogate for Therapeutic equivalence

Abstract

Healthcare expenses are on the rise globally and more evident in developing countries newlinewhere a substantial portion of disease management goes to the cost of medicines. newlineVariations in prescribing practices and/or inter-changeability of innovator medicines newlinewith generic products are frequently practiced by physicians and pharmacists with an newlineaim to reduce the high cost of medicines. A generic drug product is usually marketed newlineand manufactured after the expiry of the innovator patent. As a consequence, generic newlinedrug products are generally cheaper in price than the innovator since generic newlinemanufacturers do not have to undertake the expensive and time-consuming initial newlinerigorous research done by innovator companies when developing new medicines. newlineGeneric products are usually pharmaceutical equivalents which are bioequivalent with newlinethe innovator product and hence presumed to be interchangeable. Generic products newlinemust therefore be identical in dose, strength, route of administration, safety, efficacy, newlineand intended use. International regulatory agencies provide guidelines which newlinerecommend that if an active pharmaceutical ingredient newline( newlineAPI newline) newline meets certain physico- newlinechemical criteria, including, importantly solubility, a bioequivalence assessment newlinecomparing the generic product with the innovator product may be used to obtain market newlineapproval thereby removing the need for expensive and time-consuming clinical studies newlinein human patients. Furthermore, if bioequivalence can be established by using in vitro newlinedissolution and correlated with the in vivo release of the API, a so-called Biowaiver newlinemay be possible. This implies that in vivo bioequivalence studies in humans can be newlinewaived, and such waivers are generally based on the Biopharmaceutics Classification newlineSystem newline( newlineBCS newline) newline. In 2000, the U.S. Food and Drug Administration newline( newlineFDA) newline issued a newlineGuidance for Industry whereby a biowaiver could be obtained for certain generic newlineI newlineABSTRACT newlineproducts on the basis of in vitro studies. In 2006, the WHO released a bioequivalence newlineguidance which included