Influence of water-soluble polymers on the dissolution of nifedipine solid dispersions with combined carriers.
The objective of this investigation was to clarify the influence of water-soluble polymers on the dissolution behavior of nifedipine from solid dispersions with combined carriers. All the solid dispersions of nifedipine were prepared by the fusion method using nicotinamide and 4 different water-soluble polymers, hydroxypropylmethyl-cellulose (HPMC), polyvinylpyrrolidone (PVP), partially hydrolyzed polyvinyl alcohol (PVA) and pullulan. HPMC, PVP or PVA dissolved in the fused liquid of nicotinamide and operated efficiently on the amorphous formation of nifedipine in solid dispersions. In dissolution studies, the drug concentration for these dispersions increased to more than twice intrinsic drug solubility. The rank order of the drug concentration was HPMC > PVP > PVA. However, since pullulan did not dissolve in the fused nicotinamide, nifedipine was present as a crystalline state in the solid dispersion; the supersaturation behavior of the drug was scarcely observed. The compatibility, namely, the solubility and miscibility, between nicotinamide or nifedipine and the polymers, was determined by differential scanning calorimetry using the mixtures treated with fusing and subsequent rapid cooling. Both HPMC and PVP exhibited high compatibility not only with nicotinamide but also with nifedipine. The crystallization behavior of nifedipine from a supersaturated solution containing nicotinamide or the polymers was studied. The inhibitory effect of HPMC or PVP for drug crystallization was evident, which would be related not to the solubilizing effect but to the adhesive force of the polymer for the drug. Therefore, it was understood that the use of a polymer with high compatibility and adhesion with nifedipine provides a high supersaturation level of the drug in dissolution. Further, the solubility parameter was found to be useful for selecting a suitable polymer as a component of combined carriers.
Suzuki
H
H
Fuji Laboratory, Janssen-Kyowa Co., Ltd, Shizuoka, Japan.
Sunada
H
H
D002121:Calcium Channel Blockers / Q000737:chemistry*; D004337:Drug Carriers; D004347:Drug Interactions; D009536:Niacinamide / Q000737:chemistry; D009543:Nifedipine / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D012995:Solubility; D013696:Temperature
D002121:Calcium Channel Blockers; D004337:Drug Carriers; D011108:Polymers; D009536:Niacinamide; D009543:Nifedipine