ABSTRACT
Based on an elementary osmotic pump, controlled release systems of diclofenac sodium (DS) were designed to deliver the drug in a zero-order release pattern. Osmotic pump tablets containing 100 mg DS were prepared and coated with either semipermeable (SPM) or microporous (PM) membranes. The tablet coats were composed of hydrophobic triacetin (TA) or hydrophilic polyethylene glycol 400 (PEG 400) incorporated in cellulose acetate (CA) solution, for SPM and PM, respectively. Variable tablet core compositions such as swelling polymers (PEO and HPMC) and osmotic agents (lactose, NaCl, and KCl) were studied. An optimized, sensitive and well controlled in vitro release design, based on the flow-through cell (FTC), was utilized to discriminate between preparations. The results revealed that the presence of PEG 400 in the coating membrane accelerated the drug release rate, while TA suppressed the release rate of DS. In the case of SPM, the amount of DS released was inversely proportional to the membrane thickness, where 5% (w/w) weight gain gave a higher DS release rate than 10% (w/w). Results of different tablet core compositions revealed that the release rate of DS decreased as PEO molecular weight increased. HPMC K15M showed the lowest DS release rate. The presence of lactose, KCl, or NaCl pronouncedly affected DS release rate depending on polymer type in the core. Scanning electron microscopy (SEM) confirmed formation of pores in the membrane that accounts for faster DS release rate. These results revealed that DS could be formulated as an osmotic pump system with a prolonged, zero-order release pattern.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/chemistry , Diclofenac/chemistry , Membranes, Artificial , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Cellulose/analogs & derivatives , Cellulose/chemistry , Chemistry, Pharmaceutical , Delayed-Action Preparations , Diclofenac/administration & dosage , Excipients/chemistry , Hydrophobic and Hydrophilic Interactions , Hypromellose Derivatives , Kinetics , Lactose/chemistry , Methylcellulose/analogs & derivatives , Methylcellulose/chemistry , Microscopy, Electron, Scanning , Osmosis , Plasticizers/chemistry , Polyethylene Glycols/chemistry , Porosity , Potassium Chloride/chemistry , Sodium Chloride/chemistry , Solubility , Surface Properties , Tablets , Technology, Pharmaceutical/methods , Triacetin/chemistryABSTRACT
Nifedipine (NF) is a poorly water-soluble drug, of low and irregular bioavailability after oral administration. Although some reports have attempted to improve the dissolution of NF using solid dispersions and solubilizers, little literature information is available on the in vivo performance of such preparations. The aim of the present work was to improve the therapeutic efficacy of NF via incorporation into different types of carriers, and to investigate their in vitro dissolution and bioavailability in rabbits. Nifedipine solid dispersions were prepared by fusion, solvent, and freeze-drying methods with polyethylene glycol (PEG) 6000 and PEG monomethylether 5000 (PEG MME 5000). Complexation of NF with beta-cyclodextrin (beta-CyD) and solubilization by sodium lauryl sulfate (SLS) have also been studied. The dissolution was determined by the flow-through cell in order to maintain perfect sink conditions. The solid dispersions resulted in a significant increase in the dissolution rate as compare to pure drug. The highest NF dissolution rate was obtained from solid dispersions containing 95% PEG 6000 prepared by the solvent method. While, unexpectedly, the highest absorption in rabbits was obtained from 95% PEG 6000 prepared by the fusion method. Compared to SLS, beta-CyD gave higher in vitro and in vivo values. Differential scanning calorimetry (DSC) and powder x-ray diffractometry indicated that NF in solid dispersions is homogeneously distributed, and no drug crystallized out of the system. The DSC thermograms of NF-beta-CyD complex and NF/SLS solid mixture showed a decrease in the NF endothermic peak. The x-rays showed different diffraction patterns of pure NF and pure carrier, suggesting the formation of a new solid form.
Subject(s)
Chemistry, Pharmaceutical/methods , Nifedipine/pharmacokinetics , Administration, Oral , Animals , Area Under Curve , Biological Availability , Calorimetry, Differential Scanning , Chromatography, High Pressure Liquid , Drug Carriers , Half-Life , Male , Nifedipine/administration & dosage , Nifedipine/blood , Polyethylene Glycols , RabbitsABSTRACT
One hundred forty-four of 166 adults with acute viral hepatitis (AVH) admitted to an Egyptian fever hospital were followed for 12 months. The hepatitis B surface antigen (HBsAg) carrier rate in 95 with hepatitis B virus (HBV) hepatitis decreased from 53% at three months to 13% at 12 months. At 12 months, 22% of the male patients had persistent HBsAg compared with only 7% of the female patients. The HBsAg carrier rate was 25% at 12 months in those with schistosomiasis compared with 9% in those with only acute HBV infection. Splenomegaly persisted in those with palpable spleens at the initial examination and others developed splenomegaly. The prevalence of splenomegaly increased from 11% on admission to 20% at 12 months in those with only AVH, and from 40% to 69% in those with concomitant schistosomiasis. Patients with concomitant schistosomiasis had higher mean values for liver function test results and a greater proportion had abnormal liver function test results during hospitalization and follow-up than those with AVH only. Concomitant schistosomiasis increased the prevalence and prolonged splenomegaly and morbidity due to AVH. Both male sex and concomitant schistosomiasis prolonged the HBsAg carrier state. We propose that AVH frequently converts uncomplicated intestinal schistosomiasis to hepatosplenic schistosomiasis.
