Preparation, characterization, and evaluation of celecoxib eutectic mixtures with adipic acid/saccharin for improvement of wettability and dissolution rate.

Celecoxib (CEL) is a selective cyclooxygenase-2 (COX-2) inhibitor therapeutically indicated for the treatment of rheumatoid arthritis, osteoarthritis, acute pain, and inflammation. However, its poor solubility and dissolution rate significantly hinders its broader application. In this study, eutectic mixtures, as binary pharmaceutical compositions of CEL with adipic acid (ADI) and saccharin (SAC), were identified through a phase diagram and Tammann's triangle intended to improve the wettability and dissolution rate of poorly water-soluble CEL. The contact angles at 0s in the liquid-solid interface were approximately θs (theta) 79.7 ±â€¯0.50° and 86.65 ±â€¯0.45° for CEL-ADI and CEL-SAC, respectively, which were much lower than the value obtained for CEL (92.05 ±â€¯0.75° θ). Moreover, a comparison of the disk intrinsic dissolution rate and powder dissolution properties demonstrated that eutectic mixtures significantly increased the dissolution rate compared with CEL and physical mixtures. A general relationship was elucidated and indicated that the dissolution rate was increased as the contact angle decreased (correlation coefficient, r = 0.9966 ±â€¯0.0031). Therefore, CEL-ADI and CEL-SAC eutectics may offer a novel formulation strategy to enhance the solubility and oral bioavailability of CEL.

Preparation and evaluation of cyclosporin A-containing proliposomes: a comparison of the supercritical antisolvent process with the conventional film method.

OBJECTIVES: The objectives of this study were to prepare cyclosporin A (CsA)-containing proliposomes using the supercritical antisolvent (SAS) process and the conventional thin film method for the comparative study of proliposomal formulations and to evaluate the physicochemical properties of these proliposomes. METHODS: CsA-containing proliposomes were prepared by the SAS process and the conventional film method, composed of natural and synthetic phospholipids. We investigated particle size, polydispersity index, and zeta potential of CsA-containing proliposomes. In addition, both production yield and entrapment efficiency of CsA in different proliposomes were analyzed. Physicochemical properties of CsA-containing proliposomes were also evaluated, using differential scanning calorimetry and X-ray diffraction. The morphology and size of CsA-containing proliposomes were confirmed, using scanning electron microscopy. We checked the in vitro release of CsA from CsA-containing proliposomes prepared by different preparation methods, comparing them with Restasis(®) as a positive control and the stability of SAS-mediated proliposomes was also studied. RESULTS: CsA-containing proliposomes formed by the SAS process had a relatively smaller particle size, with a narrow size distribution and spherical particles compared with those of conventionally prepared proliposomes. The yield and entrapment efficiency of CsA in all proliposomes varied from 85% to 92% and from 86% to 89%, respectively. Differential scanning calorimetry and X-ray diffraction studies revealed that the anhydrous lactose powder used in this formulation retained its crystalline form and that CsA was present in an amorphous form. Proliposome powders were rapidly converted to liposomes on contact with water. The in vitro release study of proliposomal formulations demonstrated a similar pattern to Restasis(®). The SAS-mediated CsA-containing proliposomes were stable on storage, with no significant changes in particle size, polydispersity index, and entrapment efficiency. CONCLUSION: These results show promising features of CsA-containing proliposomal formulations, using the SAS process for the large-scale industrial application.