Formulation and Evaluation of Oral Elementary Osmotic Pump Tablets of Sumatriptan Succinate.

Aim: In the present study, Sumatriptan succinate was formulated as oral elementary osmotic pump with a zero-order drug release profile. Methodology: The effect of different formulation variables i.e. different types of osmogens, concentrations of osmogen and concentration of coating solution were studied. The in vitro evaluation was carried out in different release media. Result: Highest percentage of drug release was observed at high concentration of mannitol i.e., 1:3 (drug: mannitol). Osmogen with low osmotic pressure (38 atm) showed 71.01% zero-order drug release for 12 hours when compared to that of the osmogen with high osmotic pressure (356 atm) which showed 67.38% of release by zero order. Conclusion: Elementary osmotic pump tablets of Sumatriptan succinate were able to deliver zero-order release up to 12 hours independent of pH of dissolution media and have overcome the problem of chronotherapeutic effect.

Preparation and Evaluation of Novel Expandable Drug Delivery System.

Aims: The purpose of this research is to develop a novel expandable gastroretentive dosage form (GRDF), based on unfolding mechanism. It consists of a drug loaded bilayer polymeric film, folded into a hard gelatin capsule. Gastric retention is achieved due to unfolding of the dosage form within 15-20 min. Furosemide is selected as the drug candidate for this work. Due to its narrow absorption window, Furosemide has to be administered to the upper parts of the intestine in order to maintain sustained therapeutic levels. This may be achieved by a GRDF. Methodology: Films were prepared by solvent-casting technique using Ethyl cellulose, HPMC E15 and Eudragit RLPO as polymers and dibutyl phthalate as the plasticizer in both layers. The film with zigzag folding in the capsule was shown to unfold in the gastric juice and provide drug release up to 12 h in the acidic medium. The films were evaluated for weight & thickness variation, mechanical properties, in vitro drug release and unfolding behavior based on the mechanical shape memory of polymers. Absence of drug polymer interaction and uniform drug dispersion in the polymeric layers was revealed by DSC, XRD studies and SEM. The GRDF location in the gastrointestinal tract was determined by X-ray studies. Results: X-ray studies revealed that the GRDF is retained in the stomach up to 6± 0.5 h in fasting condition and 8 h in fed state. Conclusion: The polymers used in the development of GRDFs were safe and proper combination of these polymers will yield a novel expandable GRDF with good in vitro drug release in acidic media, mechanical properties, and unfolding behaviour. These outcomes demonstrate that the GRDF may be used to improve furosemide therapy and can be applied to extend the absorption of other narrow absorption window drugs that require continuous input.

Enhanced Bioavailability of Nimodipine from Bioadhesive Buccal Bilayered Patches in Human Volunteers.

Aims: The objective of the present study was to develop a bioadhesive bilayered buccal patch of Nimodipine (15 mg) using Eudragit Rs 100 as secondary layer and a primary layer with Hydroxy propyl methyl cellulose and Hydroxy propyl cellulose JF. Methodology: Bilayered buccal patches were prepared by solvent casting technique. The absence of physiochemical interactions between NMDP and the polymer were investigated by differential scanning calorimetry (DSC). Bilayered buccal patches of NMDP were evaluated for in vitro drug permeation through porcine buccal membrane, in vitro drug release, moisture absorption, surface pH, mechanical properties and in vitro bioadhesion. Results: The results indicated that suitable bioadhesive bilayered buccal patches with desired permeability could be prepared. The bioavailability study was performed in healthy humans in a crossover experimental design. Bioavailability studies revealed that nimodipine possessed good buccal absorption. The relative bioavailability of the optimized buccal patch was found to be 205% in comparison to 30 mg marketed oral tablet. The formulation CC3 showed 68.84 ± 1.4% release and 46.85 ± 5.1% of drug permeated through porcine buccal membrane in 4 hr. A good correlation was seen between percentage in vitro release the extent of bioavailability for nimodine buccal patch. Conclusion: An improvement of bioavailability was obtained by buccal route to the extent of 2.05 times higher than that of oral route for NMDP. Hence, the development of a bioadhesive bilayered buccal patch for NMDP might be a promising one, as the necessary dose of drug could be decreased, resulting less side effects. Good ex vivo - in vivo correlation was obtained for NMDP.

Formulation and Evaluation of Gastroretentive Floating Tablets of Domperidone Maleate.

The low bioavailability (15%) and good solubility of Domperidone Maleate in acidic pH following oral administration favours development of a gastro retentive formulation. Gastroretentive floating matrix tablets of Domperidone Maleate were successfully prepared with hydrophilic polymers like HPMC K4M, HPMC K15M and HPMC K100M. From the Preformulation studies for drug excipients compatibility it was observed that there was no compatability problem with the excipients used in study. The drug release from most of the formulations follows fickian diffusion. From in-vivo X-ray studies, it was clearly observed that the floating tablets showed a gastric residence of nearly 4.5 hrs in fed state.

Evaluation of target concentration intervention strategy of gentamicin therapy in a malnourished patient population of south India.

BACKGROUND & OBJECTIVE: Aminoglycoside antibiotics, especially gentamicin, are widely used in suspected Gram-negative infections in India. Therapeutic drug monitoring is not commonly used for this drug in our population. We evaluated the target concentration intervention (TCI) strategy of gentamicin therapy in a predominantly malnourished patient population with lower respiratory tract infection in south India. METHODS: Patients who were prescribed gentamicin for suspected lower respiratory tract infection were randomized to any of the three groups, viz., control (CG), once daily dosing (ODD), and pharmacokinetic dosing (TCI) groups. Diagnosis was initially done by clinical evaluation and confirmed radiologically. Patients in CG received 80 mg gentamycin twice daily, ODD group received 160 mg once daily, and TCI groups received 160 mg once daily initially followed by dose revision based on serum drug levels. Blood samples were collected at peak and trough levels and assayed for gentamicin concentration. Dose adjustment was done in TCI group whereas the other groups received standard doses. Efficacy and safety were evaluated as outcome measures. RESULTS: Of the 52 patients included initially in the study, 43 (CG 20, ODD 12, TCI 11) completed the study. The doses administered to the study subjects were less than those prescribed in standard textbooks and guidelines. Patients in TCI group had their gentamicin doses revised upwardly to a dose of 4.3+/-0.6 mg/kg to achieve a peak gentamicin concentration of 12 to 15 microg/ml. Both ODD and TCI groups showed significant improvements in outcomes studied over the control group. INTERPRETATION & CONCLUSION: The results of our study indicated that once daily dosing of gentamycin was superior to multiple daily dosing in treating the lower respiratory tract infection in the study population. All patients in the ODD and TCI groups achieved satisfactory serum drug concentrations at administered doses (160 mg/day for ODD and <or= 200 mg/day for TCI group). In our study, target concentration intervention did not significantly improve the therapy outcomes. Since the study sample is small further research may be needed.

Comparison of target concentration intervention strategy with conventional dosing of digoxin.

Digoxin is a widely used drug in patients with congestive heart failure. The present study compared the quality of life of congestive heart failure patients on one year follow-up period with two different dosing of digoxin (5/7 therapy and 7/7 therapy in whom the target serum digoxin concentration is maintained). Quality of life significantly improved in intervention group thus emphasizing the need for continuous dosing of digoxin based on target concentration.