Reverse Thermal Plastic Regel Synthesis And Ophthalmic Preparations

Regel, a water soluble, low molecular weight reverse thermosensitive biodegradable block copolymer was studied in this work. Such copolymers of relatively low molecular weight and relatively high hydrophobic block polymer exist as clear solutions at, or about 5 -25 in water but ,when the temperature is raised to about body temperature (typically 37癈 for humans),spontaneously form semisolid hydrogels that contain high percentages of water entrapped in the gel network . This system can used as parenteral, ocular, topical, transdermal, vaginal, buccal, transmucosal, pulmonary, transurethral, rectal, nasal, oral, pulmonary or aural delivery vehicles.Details of the synthesis of Regel from lactic acid, glycolic acid and PEG are described. The process condition of the synthesis such as temperature, time, catalyst and pressure of reaction were studied and also optimized by means of uniform design.The synthetic product was characterized by GPC, DSC, and H-NMR. The viscosity and the phase transition temperature and other chemical and physical characteristics were determined. The acute toxicity and ophthalmic irritability were also studied. The results showed that the lower toxicity of Regel was satisfied for pharmaceutical application, and no acute irritation was observed.Most of the applications of the Regel are concerned with treatment of ophthalmic disease for its reverse thermosensitive and convenient administration combined with the favorable ocular residence time. In this study, pirenoxium was selected as a model drug, and a series of researches were carried out to development of suspensive gels with modulated phase transition temperature.The suspension quality and stability, dug release and gel dissolution were alsostudied. The suspension can keep stabilizing for a period for 3 months at 40 and a period of 5 months at 25 . According to the in vivo characteristic of ocular administration, a membraneless model was used to study the gel dissolution and drug release simultaneously. Correlation analysis demonstrated that drug release was controlled by gel erosion. Experimental and formulation factors influenced the rate of gel erosion and drug release was dependent of the preparative conditions and component of the formulation.