To improve solubility and stability of poorly water-soluble drug by using colloidal silicon dioxide as surface adsorbent in solid dispersion technique

摘要

Most of new drug entities developed have less aqueous solubility. They belong to BCS class II as they have less aqueous solubility and high permeability. For oral dosage forms bioavailability and dissolution plays important role. Poor solubility of drug affect bioavailability and dissolution of drug. Therefore, enhancing solubility of poor water-soluble drug is a challenge. There various techniques to improve solubility of drug. Solid dispersion is one of the technique to enhance solubility and dissolution rate of less soluble drugs. It is efficient and widely used technique.;Crystalline form of drug has less aqueous solubility as compare to amorphous form. Solid dispersion technique involves conversion of crystalline form of drug to amorphous therefore enhancing solubility of drug. Solid dispersion consists of 2 components, hydrophilic polymer and hydrophobic drug.;The drug in amorphous state in solid dispersion is thermodynamically less stable. The amorphous molecules have high molecular mobility and high energy. Therefore, they have high tendency to recrystallize the drug affecting solubility and dissolution of drug. Different stabilizers, porous materials or absorbents can be used to enhance stability of amorphous solid dispersion. Colloidal silicon dioxide can be used as stabilizer. Colloidal silica has high surface area and pore volume. Therefore, reduces the mobility of drug molecule and stabilize amorphous solid dispersion by preventing recrystallization of drug.;In this study fenofibrate was selected as model drug to study the enhancement in solubility and stability in solid dispersion. It is BCS Class II drug. Fenofibrate was selected as it has high tendency to crystallize and it also has very less water solubility. HPMC was selected as polymeric component of solid dispersion. HPMC is available in different grades. For this study HPMC E5 (METHOCEL LV E5) was used. Two different grades of colloidal silica were used. SYLOID 244FP and AEROSIL 200 are different grades of colloidal silica.;There are various techniques to form solid dispersion. In this study, solid dispersion was formed by using spray drying technology. BUCHI mini spray dryer B290 was used. It is solvent evaporation technique to form solid dispersion. Spray drying is a complex process and several parameters need to be adjusted. Some of the parameters like inlet air temperature, solvent; flow rate, nozzle size, drying gas air flow were kept constant to avoid variation in the experiments. Optimum ratio of drug and polymer to form solid dispersion was determined.;All solid dispersions were made keeping the ratio of drug and polymer same and both stabilizers were used in different ratio in different dispersion. All solid dispersions were further characterized by MDSC, X-ray Diffraction Pattern, FTIR. Enhancement of solubility was determined by Dissolution. Dissolution tests were carried out in sink and non-sink conditions. All solid dispersions were also subjected to accelerated stability conditions to check the stability of drug in solid dispersion.;The results form dissolution was compared to dissolution of pure drug as well as with physical mixture of drug, polymer and stabilizer and also with external solid dispersion. The MDSC, x-ray diffraction, FTIR results of stability samples after 2 weeks, 4 weeks and 6 weeks were with initial samples.;Overall it can be summarized that use of stabilizers help to improve stability as well as stability of solid dispersion. Increasing concentration of stabilizer increases rate of dissolution. Solid dispersion showed higher dissolution as compared to pure drug and physical mixtures. However, solid dispersion containing aerosil were more stable as compared to one with syloid.