Effect of Amount of Water in Dispersed Phase on Drug Release Characteristics of Dextran Microspheres Prepared by Emulsion-Solvent Evaporation Process

Abstract

The microencapsulation techniques are widely used in the pharmaceutical field.1) Among them, emulsion solvent evaporation method has taken considerable attention in recent years, and numerous methods to manipulate a drug release behavior have been reported.2) Several preparation variables influencing on the properties of microspheres have been identified, including solvent type, solvent removal rate, preparation temperature, composition and viscosity of polymer, and drug loading amount. In a previous study, we illustrated the effect of temperature-increase rate in the solvent evaporation process (referred to as the temperature-increase method hereafter) on the drug release property of the microspheres.3) In this method, the preparative vessel was heated up at the constant rate in order to evaporate the dispersed solvent. By means of the temperature-increase method, microspheres showing constant drug release were prepared over a short period of time. Although a variety of studies has been conducted, the effects of poor solvent in the dispersed phase on the physical properties and drug release characteristics are not well-documented.The aim of the current work was to evaluate the effects of poor solvent in the dispersed phase on drug release from the microspheres when the temperature-increase method was employed for the emulsion solvent evaporation process. In this study, model microspheres were prepared from theophylline (TH) and hydrophobic dextran derivative (PDME). TH was used as a representative drug since sustained-release formulations are desirable because of the short elimination half-life in humans. PDME was selected as a water-insoluble polymer; it is used for contact lenses in the industrial field. Mixtures of acetone and water were used as the dispersed phase and liquid paraffin as the continuous phase. The microspheres were characterized by their size and drug loading efficiency. The morphology of the microspheres was then observed by scanning electron microscopy. In addition, drug release was examined and its kinetics were analyzed. MATERIALS AND METHODSMaterials TH as an anhydrous form was purchased from Sigma Chemical Co. (St. Luis, MO, U.S.A.) and was used after sieving through a 200-mesh sieve (less than 75 mm). PDME was kindly donated by Meito Sangyo Co., Ltd. (Nagoya, Japan) and was used without further purification. PDME is prepared from dextran (Mw 40000) by substitution of 0.58 mol acetyl, 0.81 mol propionyl, 1.42 mol butyryl and 0.16 mol methacryloyl per anhydroglucose unit of dextran. Acetone was purchased from Wako Pure Chemical Industry, Ltd. (Osaka, Japan). Liquid paraffin conforming to JP standard was obtained from Iwaki Seiyaku Co., Ltd. (Tokyo, Japan). Sucrose-ester (DKF-10) was generously supplied by Dai-ichi Kogyo Seiyaku Co., Ltd. (Kyoto, Japan) and was used as an emulsifier. Polyoxyethylene (20) sorbitan monolaurate (Tween 20) was purchased from Wako Pure Chemical Industries, Ltd. (Osaka, Japan). Ultra purified water generated by Direct-Q (Nihon Millipore Ltd., Tokyo, Japan) was ...

Relationship between Diffusivity of Water Molecules Inside Hydrating Tablets and Their Drug Release Behavior Elucidated by Magnetic Resonance Imaging

“…Because EA is a weakly basic compound, the number of ionized amine groups reduces with increasing pH. 23) This change in ionization is accompanied by a lower yield from the polyion complex because of weaker interactions between polyion complexes. Consequently, a greater rate of drug release rate is observed in the more neutral second fluid.…”

Comparison of gastroretentive microspheres and sustained-release preparations using theophylline pharmacokinetics

“…All the microspheres, including MS-sustain, MS-float and MSadhesive, were made of PDME according to previous studies (Miyazaki et al 2003b(Miyazaki et al , 2006(Miyazaki et al , 2007. Table 2 summarizes their characteristics -product recovery, drug content and mean diameter.…”

“…Mucoadhesive microspheres prepared using a mixture of dextran sulfate and 2-diethylaminoethyl dextran as mucoadhesive polymers were retained in the stomach for a few hours after oral administration to rats, improving the bioavailability of thiamine disulfide (Miyazaki et al 2003a). The floatable microspheres were prepared from a hydrophobic dextran derivative using a poor solvent addition method (Miyazaki et al 2007). These microspheres were expected to float on the gastric fluid on the basis of results of an in-vitro floating study (Miyazaki et al 2008).…”