Improving dissolution and absorption rates of naproxen and thiamphenicol using co-evaporation method

Abstract

In order to increase dissolution and absorption rates of naproxen and thiamphenicol which have the difference of acid-base properties, coevaporates or solid dispersions of the drugs with water-soluble polymers such as polyvinylpyrrolidone (PVP) and polyethylene glycol (PEG) with different molecular weights were prepared using co-evaporation method. Dissolution of the drugs from these preparations were studied compared to the corresponding physical mixtures and pure drug alone. The influence of types and amount of carriers used on dissolution characteristic of both drugs were investigated. Furthermore, in vitro absorption and physical characterization of the coevaporates with the best dissolution were evaluated. From dissolution studies in phosphate buffer pHs 1.5, 4.5 and 7.5 similar results were observed for both naproxen and thiamphenicol that the coevaporates exhibited faster dissolution than the corresponding physical mixtures and pure drugs. The highest dissolution rate and extent of both drugs were obtained from PVP K-30 coevaporate followed by PVP K-90, PEGs 4000, 6000, and 20000 coevaporates, respectively. Moreover, decreasing the weight fraction of PVP K-30 in the coevaporates from the ratio 1:1 of drug:carrier to 1:0.25, decreased the dissolution rates of the drug from the preparations. However, there were no statistically significant difference of dissolution rates between 1:1 and 1:0.75 thiamphenicol-PVP K-30 coevaporates (p > 0.10). Hence, the best systems for enhancing the dissolution of naproxen and thiamphenicol were 1:1 naproxen-PVP K-30 and 1:0.75 thiamphenicol-PVP K-30 coevaporates, respectively. The in vitro absorption studies using Sartorious absorption simulator (SM 16750) exhibited statistically significant higher absorption of the drugs from the coevaporates as compared to the pure drugs (p > 0.05). However, significant correlation between dissolution and absorption rates were observed in thiamphenicol system only (p > 0.05).X-ray diffraction studies and differential thermal analysis of the drugs and the coevaporates showed evidences that naproxen and thiamphenicol dispersed in PVP K-30 matrix in crystalline and amorphous forms, respectively, which may explain the increasing factors of dissolution and absorption of the drugs from the coevaporates