| Ciprofloxacin hydrochloride (CP) is representative of the third generation of fluoroquinolones. It is a broad spectrum antibacterial drug with high antibacterial activity. The absorption of CP after oral administration is rapid and the distribution is wide. The aim of this work was designed to develop a kind of CP sustained-release pellets which would reduce dosing frequency, narrow the fluctuation of blood concentration and be more convenient for patients to use.Ultraviolet spetrophotometry was developed for assaying the content in the preparation and drug release from CP sustained-release pellets. According to the solubility of CP determined in different medium. When pH<5.5 the solubility is >20mg·ml-1, and when pH is near to the pKa, the solubility is <2mg·ml-1. The apparent partition coefficient in n-octanol/medium system is 0.4-1.3.Two kinds of CP pellets were prepared in a centrifugal granulator. One was prepared with MCC, lactose as dilute agent and water as moistening agent by powder layer technology, the other (tested as immediate release pellet) was prepared with MCC, lactose as dilute agent, citric acid as buffer and water as moistening agent. The dissolution profile of the two kinds of pellets indicated the dissolution of the non-buffer pellet was much slower than the buffer pellet in mediums of 7.4 >pH>5.5. Powder property of the pellets included citric acid was determined and the yield of objective pellets (18-24 mesh cut) was about 90%.A fluid-bed spray processor was adopted for the coating of the buffer pellets. The pH-dependent sustained-release pellets (T1 tested as extended release pellet) were coated with a combination of Eudragit NE30D and Eudragit L30D-55. The non-pH-dependent sustained-release pellets (T2) were coated with a combination of Eudragit RL 30D and Eudragit RS 30D. The influence factors on the release of CP from T1 and T2 were investigated. The technology and formulation of T1 and T2 were optimized, respectively. The results demonstrated that two kinds of coated pellets showed obviously sustain-release effect, and the drug release profiles in vitro followed Higuchi(T1) and first-order kinetics (T2).HPLC method was performed to detect the concentration of CP in plasma of dogs and in urine of healthy volunteers. The plasma concentration of CP in six dogs were tested after a single oral administration of T1 with commercial tablets as a reference preparation. Cmax, Tmax and MRT of T1 were (3.05±0.67)μg·mL-1, (6.00±0.0)h, (12.23±2.92)h, respectively, and the relative bioavailability was (97.10±9.61)%. The results showed that T1 and commercial tablets were bioequivalent, The capsules filled with 35% immediate release pellets and 65% extended release pellets(T1) were of oral administration of six healthy volunteers. The urinary concentration of CP was tested: (dxu/dt)max=(25.92±3.70) mg·mL-1, Tmax=(4.17±1.60)h, MRT=(9.65±1.58)h, and the relative bioavailability was (101.04±11.36)%, respectively. The results indicated this dosage form had an improved pharmaceutical quality, which might enhance its therapeutic profile.
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