Studies On Erythromycin Self-Microemulsifying Drug Delivery System

Erythromycin Self-microemulsifying drug delivery system (EM-SMEDDS), choosing Erythromycin as the drug and oil and surfactants as vehicles , is thermodynamically stable SMEDDS. The Self-microemulsifying drug delivery system are described as mixtures of oil, surfactant, cosurfactant and drug. The principal characteristic of these systems form fine oil-in-water microemulsions upon mild agitation following diluted by aqueous phase, with mean droplet size less than 100nm. SMEDDS can improve the bioavailability and the absorption of poorly soluble drugs. In recent years, much attention has been paid to the study. Most oral dosage forms of Erythromycin had low bioavailability. Due to their poor solubility properties in water, Erythromycin could hardly dissolve in gastrointestinal fluids. Erythromycin is deemed unsuitable for oral administration for the poor bioavailability and low water solubility. Therefore,SMEDDS was selected as the carrier to prepare EM-SMEDDS to increase the dissolution, absorption and bioavailability of Erythromycin. The objective of our research is made up of four topics: PART ONE PREFORMULATION STUDYFirst of all, UV spectrophotometry analytic for microemulsions, Erythromycin was analyzed with the wave length at 482 nm after adding the 75% sulphuric acid solution and keeping it in 75±5℃water for 30min. The logarithm of apparent partition coefficients of Erythromycin in n-octanol/o.1mol·L-1HCL,n-octanol/pH 6.8 PBS and n-octanol/Water system were 1.09,1.28 and 1.62 respectively, The Log P reduces with the pH of aqueous phase means that the solubility of Erythromycin in aqueous phase increases.PART TWO THE OPTIMIZATION OF FORMULATION AND PREPARATION FOR EM-SMEDDSThe balance solubility of EM in different oil Phase,surfactant and cosurfactant were assayed, which higher than another were selected. Pseudo-ternary phase diagrams were constructed. The optimal SMEDDS were obtained by comparing the self-emulsifying domain and by the evaluation of the resultant emulsion's appearance. The optimal SMEDDS was IPM (30~40%),the mixed surfactant was made up of Cremopher EL and LAS (Cremopher EL 65~75%).Through the uniform design, we investigated the effects of the vehicle contents,temperature,and drug loading on the self-emulsifying efficiency, which self-emulsifying efficiency included the self-emulsifying time, mean droplet size and the distribution of droplet size .All results brought us a best formulation of EM-SEDDS.PART THREE THE EVALUATION OF PHARMACY FOR EM-SMEDDSThe zeta potential of blank SMEDDS and EM-SMEDDS in water are both close to 0mV, which indicated the stabilization of them. The present findings introduced the hot-cold cycle for 7 days and observed at room temperature for 6 months, which the physico-chemical property of EM-SMEDDS was stabilitated.We study the dissolution of EM-SMEDDS by bulk-equilibrium reverse dialysis bag technique. The results show that the formulations could release fast and completely, and the cumulated release of the formulations were above 64.74% at 30min, above 96.65% at 120min ,and drug release slowly after 30 min. Zero-order equation, frist-order equation, higuchi equation, weibull equation, Hixon-Crowell were used to calculate drug release kinetics. The results showed that the drug release elucidating with Hixon-Crowell equation were best.PART FOUR THE INITIAL STUDY IN PHARMACOKINETICS OF EM-SMEDDSThe absorption kinetics and permeability rate constants (ka) were investigated by the in situ perfusing method in rats,and the concentration of EM was determined by UV.The results indicated that EM-SEDDS can be absorbed in the whole small intestinal segments. And the ka of EM-SMEDDS at duodenum, jejunum and ileum were 1.03±0.07, 1.63±0.06 and 1.9±0.22h-1 respectively. The results also showed that the Ka of EM-SMEDDS was step-by-step increase successively according to duodenum, jejunum and ileum. Compared the Ka of EM-SMEDDS with EM-suspension, we found that EM-SMEDDS can be better absorbed than EM-suspension in the small intestine, which demonstrated the SMEDDS will improve the absorption of EM by oral administration.