Approaches to improve dissolution of capsule containing a poorly water-soluble drug: Mefenamic acid
Keywords:mefenamic acid, capsule dissolution, poorly water-soluble drug
A poorly water-soluble drug, mefenamic acid (MA), in powder or granule forms was formulated in capsule dosage form. Hydrophilic and hydrophobic diluents, lactose and dibasic calcium phosphate (DCP) respectively, were used in capsules containing MA granules for preparation with polyvinylpyrrolidone K30 as a binder. The capsules containing MA granules provided faster drug dissolution profiles than did the capsules containing MA powder. Faster capsule dissolution was obtained when lactose was used as a diluent, instead of DCP, in capsules containing MA granules. Incorporation of a capsule disintegrant, sodium starch glycolate (Explotabâ), into the capsule consisting of MA granules and DCP resulted in increasing dissolution of the MA capsule. However, no obvious dissolution improvement was observed when Explotabâ was employed as disintegrant in the capsule consisting of MA granules and lactose. For the capsules containing MA granules, DCP and Explotabâ, inclusion of a surfactant, sodium lauryl sulfate (SLS), into the formulation caused further improvement in capsule dissolution. The influences of Explotabâ and SLS on dissolution of MA capsules prepared from MA powder and MA granules (with lactose or DCP as diluent) were investigated using a two-level full factorial experimental design. The use of Explotabâ and SLS in the capsules consisting of MA powder yielded greater dissolution enhancing effects than their use in the capsules consisting of MA granules and each diluent. The main and interaction effects of Explotabâ and SLS contents on capsule dissolution were identified using multiple linear regression analysis. The contour plots of the equations representing the relationships between the two capsule dissolution parameters, reflecting onset and completeness of capsule dissolution, and the contents of Explotabâ and SLS utilized in the MA capsule formulations were constructed. From these relationships, the optimum amounts of Explotabâ and SLS in the MA capsules requiring fast dissolution can be determined.
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