Thiamphenicol Ph Sensitive Eye Gel

The purpose of this paper was to develop a pH-triggered in situ gelling ophthalmic delivery system of thiamphenicol(TAP).Polyacrylic acid (Carbopol) and hydroxypropylmethylcellulose (HPMC) were used as the gelling agent. The developed system is able to freely fluid at non-physiological condition, also undergo in situ phase transition to form strong gel and sustain drug release at physiological condition.The properties of TAP such as solubility, oil/water partition coefficient, stability in phosphate buffer (pH4.0)were studied .TAP/HP-β-CD complex was prepared to improve the solubility and stability of TAP and proved by DSC. The solubility is only 1.32 mg/mL and oil/water partition coefficient is 1.08 in phosphate buffer (pH4.0). The solubility of TAP/HP-β-CD is about 11.8-folds and stability in phosphate buffer (pH4.0)is better than that of TAP.The formulation screening was performed using fluidity and gelling capacity as indices. The best formulation of TAP pH-triggered in situ gelling was 0.25%TAP, 0.3%Carbopol, 1.0%HPMC , 0.01%BKC , 0.9%NaCl.The rheological studies showed that the Carbopol/HPMC solution indicated a Newtonian flow behavior at non-physiological condition and demonstrated a pseudoplastic behavior at physiological condition. The in vitro release of TAP was sustained released. The sol-gel transition pH was about 5.3.The initial stability and ocular irritation investigation of TAP pH-triggered in situ gelling was carried out. The results indicated the formulation of TAP was more stable at low temperature than at high temperature, and was non-irritant either single or multiple dose.The in vivo evaluation was made by determination of the concentration-time curve of TAP in tear fluid by means of HPLC-MS, The results indicated that gels may be retained in the pre-corneal area for more prolonged period than drops , and improve ocular bioavailability.