Design of sustained release pellets of ferrous fumarate using cow ghee as hot-melt coating agent.

INTRODUCTION: The objective of the present study was to design ferrous fumarate (FF) sustained release (SR) pellets using of cow ghee (CG) as an important hot-melt coating (HMC) agent. MATERIALS AND METHODS: The pellets were coated by HMC technique using CG and ethyl cellulose composition by conventional coating pan without the use of spray system. FF formulated as pellets and characterized with regard to the drug content and physico-chemical properties. Stability studies were carried out on the optimized formulation for a period of 6 months at 40 ± 2°C and 75 ± 5% relative humidity. RESULTS: Pellets with good surface morphology and smooth texture confirmed by stereo micrographs. HMC is easy, efficient, rapid and simple method since virtually no agglomeration seen during coating. In-vitro release from pellets at a given level of coating and for present pellet size was dependent upon the physico-chemical property of the drug and mostly aqueous solubility of the drug. The selection of optimized FF formulation was confirmed by comparing percent cumulative drug release with theoretical release profile. Formulation F2 had difference factor (f 1) and similarity factor (f 2) values was found to be 5 and 66 respectively. F2 showed SR of drug for 8 h with cumulative per cent release of 98.03 ± 4.49%. Release kinetics indicates approximately zero order release pattern. HMC pellets were stable during the course of stability study. CONCLUSIONS: By means of HMC using CG and ethyl cellulose, SR pellets containing FF were successfully prepared.

Novel biopolymers as implant matrix for the delivery of ciprofloxacin: biocompatibility, degradation, and in vitro antibiotic release.

The purpose of this study was to investigate the in vitro-in vivo degradation and tissue compatibility of three novel biopolymers viz. polymerized rosin (PR), glycerol ester of polymerized rosin (GPR) and pentaerythritol ester of polymerized rosin (PPR) and study their potential as implant matrix for the delivery of ciprofloxacin hydrochloride. Free films of polymers were used for in vitro degradation in PBS (pH 7.4) and in vivo in rat subcutaneous model. Sample weight loss, molecular weight decline, and morphological changes were analyzed after periodic intervals (30, 60, and 90 days) to monitor the degradation profile. Biocompatibility was evaluated by examination of the inflammatory tissue response to the implanted films on postoperative days 7, 14, 21, and 28. Furthermore, direct compression of dry blends of various polymer matrices with 20%, 30%, and 40% w/w drug loading was performed to investigate their potential for implant systems. The implants were characterized in terms of porosity and ciprofloxacin release. Biopolymer films showed slow rate of degradation, in vivo rate being faster on comparative basis. Heterogeneous bulk degradation was evident with the esterified products showing faster rates than PR. Morphologically all the films were stiff and intact with no significant difference in their appearance. The percent weight remaining in vivo was 90.70 +/- 6.2, 85.59 +/- 5.8, and 75.56 +/- 4.8 for PR, GPR, and PPR films respectively. Initial rapid drop in Mw was demonstrated with nearly 20.0% and 30.0% decline within 30 days followed by a steady decline to nearly 40.0% and 50.0% within 90 days following in vitro and in vivo degradation respectively. Biocompatibility demonstrated by acute and subacute tissue reactions showed minimal inflammatory reactions with prominent fibrous encapsulation and absence of necrosis demonstrating good tissue compatibility to the extent evaluated. All implants showed erosion and increase in porosity that affected the drug release. Increase in drug loading significantly altered the ciprofloxacin release in extended dissolution studies. PPR produced drug release >90% over a period of 90 days promising its utility in implant systems. The results demonstrated the utility of novel film forming biopolymers as implant matrix for controlled/sustained drug delivery with excellent biocompatibility characteristics.

Evaluation of sedative and anticonvulsant activities of Unmadnashak Ghrita.

'Unmadnashak Ghrita' (UG) is a ayurvedic formulation containing Ferula narthex (6 g), Gardenia gummifera (6 g), Ellataria cardamom (6 g), Bacopa monneri (6 g), and cow's ghee (clarified butter fat) (76 g). In the present study, neuropharmacological activities of UG were evaluated for its gross behavioural effect, pentobarbitone sleeping time, spontaneous locomotor activity, antagonism to amphetamine induced hyperlocomotor activity, analgesic activity by tail flick test, rota-rod performance (motor coordination test), maximal electroshock (MES) induced seizures, and pentylenetetrazol (PTZ) induced convulsions in mice. The formulation showed CNS-depressant activity in gross behavioural test, potentiated pentobarbitone sleeping time and there was significant decrease in spontaneous locomotor count in mice. The formulation also antagonized the behavioral effects of CNS-stimulant drug amphetamine, and showed analgesic effect in mice. UG failed to affect the motor coordination test. The formulation also protected mice from MES and PTZ induced convulsions. These results suggest that UG has CNS-depressant and anticonvulsant activity in mice.

Evaluation of hepatoprotective effect of Amalkadi Ghrita against carbon tetrachloride-induced hepatic damage in rats.

Amalkadi Ghrita (AG), a polyherbal formulation, was evaluated for its hepatoprotective activity against carbon tetrachloride (CCl4)-induced hepatic damage in rats. The hepatoprotective activity of AG was evaluated by measuring levels of serum marker enzymes like serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), and acid phosphatase (ACP). The serum levels of total proteins and bilirubin were also estimated. The histological studies were also carried out to support the above parameters. Silymarin was used as standard drug. Administration of AG (100 and 300 mg/kg, p.o.) markedly prevented CCl4-induced elevation of levels of serum GPT, GOT, ACP, ALP, and bilirubin. The decreased level of total proteins due to hepatic damage induced by CCl4 was found to be increased in AG-treated group. The results are comparable to that of silymarin. A comparative histopathological study of liver exhibited almost normal architecture, as compared to CCl4-treated group. Hepatoprotective effect of AG is probably due to combined action of all ingredients.

Biodegradation and in vivo biocompatibility of rosin: a natural film-forming polymer.

The specific aim of the present study was to investigate the biodegradation and biocompatibility characteristics of rosin, a natural film-forming polymer. Both in vitro as well as in vivo methods were used for assessment of the same. The in vitro degradation of rosin films was followed in pH 7.4 phosphate buffered saline at 37 degrees C and in vivo by subdermal implantation in rats for up to 90 days. Initial biocompatibility was followed on postoperative days 7, 14, 21, and 28 by histological observations of the surrounding tissues around the implanted films. Poly (DL-lactic-co-glycolic acid) (PLGA) (50:50) was used as reference material for biocompatibility. Rate and extent of degradation were followed in terms of dry film weight loss, molecular weight (MW) decline, and surface morphological changes. Although the rate of in vitro degradation was slow, rosin-free films showed complete degradation between 60 and 90 days following subdermal implantation in rats. The films degraded following different rates, in vitro and in vivo, but the mechanism followed was primarily bulk degradation. Rosin films demonstrated inflammatory reactions similar to PLGA, indicative of good biocompatibility. Good biocompatibility comparable to PLGA is demonstrated by the absence of necrosis or abscess formation in the surrounding tissues. The study provides valuable insight, which may lead to new applications of rosin in the field of drug delivery.

Study of novel rosin-based biomaterials for pharmaceutical coating.

The film forming and coating properties of Glycerol ester of maleic rosin (GMR) and Pentaerythritol ester of maleic rosin (PMR) were investigated. The 2 rosin-based biomaterials were initially characterized in terms of their physicochemical properties, molecular weight (Mw), and glass transition temperature (Tg). Films were produced by solvent evaporation technique on a mercury substrate. Dibutyl sebacate plasticized and nonplasticized films were characterized by mechanical (tensile zzzz strength, percentage elongation, and Young's modulus), water vapor transmission (WVT), and moisture absorption parameters. Plasticization was found to increase film elongation and decrease the Young's modulus, making the films more flexible and thereby reducing the brittleness. Poor rates of WVT and percentage moisture absorption were demonstrated by various film formulations. Diclofenac sodium-layered pellets coated with GMR and PMR film formulations showed sustained drug release for up to 10 hours. The release rate was influenced by the extent of plasticization and coating level. The results obtained in the study demonstrate the utility of novel rosin-based biomaterials for pharmaceutical coating and sustained-release drug delivery systems.