Quasi Emulsion Research Articles

Design of Agglomerated Crystals of Ibuprofen During Crystallization: Influence of Surfactant

Objective(s) Ibuprofen is a problematic drug in tableting, and dissolution due to its poor solubility, hydrophobicity, and tendency to stick to surface. Because of the bad compaction behavior ibuprofen has to be granulated usually before tableting. However, it would be more satisfactory to obtain directly during the crystallization step crystalline particles that can be directly compressed and quickly dissolved. Materials and Methods Crystallization of ibuprofen was carried out using the quasi emulsion solvent diffusion method in presence of surfactant (sodium lauryl sulfate (SLS), Tween 80). The particles were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (XRPD) and were evaluated for particle size, flowability, drug release and tableting behavior. Results Ibuprofen particles obtained in the presence of surfactants consisted of numerous plate- shaped crystals which had agglomerated together as near spherical shape. The obtained agglomerates exhibited significantly improved micromeritic properties as well as tableting behavior than untreated drug crystals. The agglomerates size and size distribution was largely controlled by surfactant concentration, but there was no significant influence found on the tableting properties. The dissolution tests showed that the agglomerates obtained in presence of SLS exhibited enhanced dissolution rate while the agglomerates made in the presence of Tween 80 had no significant impact on dissolution rate of ibuprofen in comparison to untreated sample. The XRPD and DSC results showed that during the agglomeration process, ibuprofen did not undergo any polymorphic changes. Conclusion

エマルション-溶媒-拡散法による薬剤粉末の球形晶析造粒の挙動, プロセスの改良及び回分式閉回路システムの提案

Agglomeration mechanism of the spherical crystallization of a water soluble drug by the emulsion solvent diffusion method was investigated with a mixed system of two or three partially miscible solvents, i. e., bridging liquid-poor solvent system or good solventbridging liquid-poor solvent system. When bridging liquid (or plus good solvent) solution of the drug was poured into poor solvent (=dispersing medium) under agitation, quasi emulsion droplets of bridging liquid or good solvent were produced. The diffusion of bridging liquid or good solvent from the emulsion droplet into the dispersing medium induced the crystallization of drug, which was clearly monitored by an X-ray diffraction analysis. Seeding the drug crystals to the system enhanced the solidification of emulsion droplets, resulting improved agglomeration. The agglomerated crystals had the most thermodynamically stable crystalline form. Both hydrophilic and hydrophobic polymers could be coprecipitated into the agglomerated crystals to modify the physicochemical properties of raw crystals of the drug. A closed circuit batch operation system was proposed to use repeatedly the dispersing medium recovered after each operation for industrialization.

Development of Agglomerated Crystals of Irbesartan by Spherical Crystallization Technique for Enhancing the Micromeritic and Solubility Property

Irbesartan is practically insoluble in water. The aim of the present study is to increase the solubility of irbesartan by spherical crystallization method and formulate it into oral tablets. Three different solvents such as N, N dimethyl formamide, chloroform, and water were selected. Spherical crystals were prepared by using β-cyclodextrin andHP-β-cyclodextrin in various ratios by quasi emulsion solvent diffusion method. Spherical agglomerates are prepared and converted into oral dispersible tablets by direct compression technique. Various super disintegrating agents such as SSG, Croscarmalose and crospovidone F36 of 1:3 ratios were utilized and results suggest high dissolution efficiency of 98%. Analysis of variance showed a significance of p<0.05, which indicates the importance of co-processing parameters variability within the specified limits