Abstract
Solubility and dissolution rate of drugs are of major importance in pre-formulation studies of pharmaceutical dosage forms. The solubility improvement allows the drugs to be potential biowaiver candidates and may be a good way to develop more dose-efficient formulations. Solubility behaviour of lamivudine, stavudine and zidovudine in individual solvents (under pH range of 1.2 to 7.5) was studied by equilibrium solubility and intrinsic dissolution methods. In solubility study by equilibrium method (shake-flask technique), known amounts of drug were added in each media until to reach saturation and the mixture was subjected to agitation of 150 rpm for 72 hours at 37 ºC. In intrinsic dissolution test, known amount of each drug was compressed in the matrix of Wood's apparatus and subjected to dissolution in each media with agitation of 50 rpm at 37 ºC. In solubility by equilibrium method, lamivudine and zidovudine can be considered as highly soluble drugs. Although stavudine present high solubility in pH 4.5, 6.8, 7.5 and water, the solubility determination in pH 1.2 was not possible due stability problems. Regarding to intrinsic dissolution, lamivudine and stavudine present high speed of dissolution. Considering a boundary value presented by Yu and colleagues (2004), all drugs studied present high solubility characteristics in intrinsic dissolution method. Based on the obtained results, intrinsic dissolution seems to be superior for solubility studies as an alternative method for biopharmaceutical classification purposes.
Highlights
Biopharmaceutical Classification System (BCS) is a scientific tool proposed by Amidon and colleagues (1995) and it is based on aqueous solubility and intestinal permeability characteristics of drug substances
In order to set a reliable condition for BCS classification of compounds and considering that small intestine is the major site for drug absorption, this study has considered the pH range of 1.2 to 7.5 for equilibrium solubility and intrinsic dissolution studies
The BCS was developed based on two properties: solubility/dissolution rate and intestinal permeability of drugs
Summary
Biopharmaceutical Classification System (BCS) is a scientific tool proposed by Amidon and colleagues (1995) and it is based on aqueous solubility and intestinal permeability characteristics of drug substances. Thereby, the drugs can be classified into four classes: class I (high solubility and high permeability), class II (low solubility and high permeability), class III (high solubility and low permeability), and class IV (low solubility and low permeability) (Amidon et al, 1995; Lennernäs, Abrahamsson, 2005; Löbenberg, Amidon, 2000; United States, 2000). The BCS is used to develop new pharmaceutical formulations, it assists in biowaiver processes for class I drugs as a regulatory tool and it predicts the in vivo behavior of a compound (Amidon et al, 1995; EMA, 2001; United States, 2000). In 2000, a guide published by FDA (Food and Drug Administration), based on BCS, provides waiver for bioavailability and bioequivalence studies in vivo for immediate release dosage forms (class I drugs) (United States, 2000). FDA guidance (2000) recommends solubility and permeability tests in order to classify drugs according to BCS (United States, 2000) It is possible to reduce time, costs and exposure of healthy volunteers to develop new medicinal products (Chen, Yu, 2009; Cook, Addicks, Wu, 2008; Lennernäs, 2007; Lennernäs, Abrahamsson, 2005; Lindenberg, Kopp, Dressman, 2004; Lobenberg, Amidon, 2000; United States, 2000).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
