Lamivudine

The objective of the study was to develop an oral controlled release drug delivery system of Lamivudine using the sublimation method. Camphor was used as the sublimation material to prepare gastro retentive tablets that are low-density and easily floatable. Camphor was changed to pores in the tablet during the sublimation process. Floating properties of tablets and tablet density were affected by the sublimation of camphor. Release profiles of the drug from the gastro retentive tablets were affected by tablet density/porosity. The effects of different formulation variables HPMC and the effects of different concentrations were studied. The in vitro evaluation was carried out and it was found that the drug release was affected by different concentrations of polymers used. The highest percentage of drug release (96.89±0.83) was observed with xanthan polymer and followed diffusion with erosion mechanism (Non-Fickian transport).

This study aimed to develop hydrophilic matrix based controlled release  gastroretentive drug delivery system of Lamivudine floating matrix tablets, which after oral administration are designed to prolong the gastric residence time, increase the drug bioavailability and diminish the side effects of irritating drugs. FTIR studies revealed that there is no interaction between the drug and polymers used for the formulation. Among all the formulations F21 containing HPMC K100M, Carbopol 934P, Polyox WSR 303 and sodium bicarbonate, as gas generating agent was selected as optimized formulation based on physico chemical properties, floating lag time (34 sec) and total floating time (>24 h). From in vitro dissolution studies, the optimized formulation F21 showed drug release of 99.36±5.36%, whereas 92.36±5.02% of the drug was released from the marketed product within 24h. From in vivo bioavailability studies, after oral administration of floating tablet containing 100 mg Lamivudine, the Cmax, Tmax, and AUC0–∞ of optimized gastroretentive formulation were found to be 32.11±3.16 µg/mL, 8.00±1.26 h and 225±28.14 µg*h/ml, respectively. Cmax and AUC values of optimized formulation were found to be significantly higher than of marketed product, where longer gastric residence time is an important condition for prolonged or controlled drug release and also for improved bioavailability. Hence, gastro retention can be a promising approach to enhance bioavaiilability of Lamivudine with narrow absorption window in upper GIT.

A new, simple, rapid, selective, precise and accurate isocratic reverse phase ultra performance liquid Chromatography assay method has been developed for estimation of Lamivudine in tablet formulations. The separation was achieved by using column Acquity UPLC BEH Phenyl (100×2.1mm, 1.7µm), in mobile phase consisted of pH 3.8 ammonium acetate buffer and methanol. The flow rate was 0.5mL.min-1 and the separated Lamivudine was detected using UV detector at the wavelength of 277 nm. The retention time of Lamivudine was noted to be 2.50 min respectively, indicative of rather shorter analysis time. The method was validated as per ICH guidelines. The proposed method was found to be accurate, reproducible, and consistent.

The present study was aimed to develop and optimize extended release (ER) matrix tablets of Lamivudine trilayer tablets to achieve zero-order drug release for prolonged period of time. Lamivudine tablets were prepared by direct compression and consist of middle active layer with different grades of HPMC, MCC and PVP K30, upper and lower layers were prepared with Carnauba wax, Xanthan gum, EC and MCC. The tablets were also evaluated for physicochemical characteristics and release kinetics. The physicochemical characteristics of the prepared tablets were satisfactory. The developed drug delivery systems showed prolonged drug release rates over a period of 24 h. The release profile of the optimized formulation (HF23) was described by the Zero-order and Higuchi model. The results indicate that the approach used could lead to a successful development of extended release formulation of short biological half-life drug. These results also demonstrated the suitability of three-layered tablet formulation of Lamivudine to provide controlled release for prolonged period of time and improved linearity for Lamivudine in comparison to marketed product in the effective management of AIDS with patient compliance.

An 18 years old male patient with history of RVD (+ve) on ART reported generalized weakness, body pains, head ache, and loose motions 3 episodes since one week. Acute pancreatitis due to anti-retro viral therapy was diagnosed. Lamivudine was most probable causal agent. Pancreatitis was confirmed by ultra sound scan of abdomen.

An accurate, precise and reproducible RP-HPLC method for the simultaneous determination of Lamivudine and Raltegravir in the bulk API dosage form has been developed and validated. Chromatographic separation was carried out on Agilent C18 (100×4.6mm, 3.5u particle size) column using mobile phase composed of phosphate buffer (PH3.0): acetonitrile (ACN) in ratio 60:40 at a flow rate of 0.8ml/min. The analyte was monitored using DAD detector at 231nm. The retention times were found to be 1.12 and 4.08 for Lamivudine and Raltegravir respectively. The linearity for each were found in the range 10-60µg/ml and their regression values are 0.998 and 0.999 respectively. The developed method was validated as per ICH guidelines.

An accurate, precise and reproducible high performance liquid chromatographic method was developed for the simultaneous estimation of lamivudine, zidovudine and nevirapine in pharmaceutical dosage forms. Phenomenex C18 column (250 x 4.6 mm; 5µ) was employed for the separation of drugs. A mixture of 0.02 M trichloroacetic acid (6.8 pH) and methanol in the ratio of 40:60 v/v was used as the mobile phase and pumped at a flow rate of 1ml/min. The detection wavelength was set at 265 nm. The linearity of quantification was observed in the range of 7.5-112.5, 10-150 and 15-225 μg/ml for lamivudine, zidovudine and nevirapine respectively. The proposed method was validated according to ICH guidelines. The method was found to be suitable for simultaneous and accurate determination of these drugs in tablet dosage forms without any interference from the excipients.

An accurate, precise and reproducible high performance liquid chromatographic method was developed for quantitative estimation of abacavir, lamivudine and zidovudine simultaneously in tablet dosage forms. Separation of the drugs was achieved within 15.0 min on a Hichrom RP-select B column (250 x 4.6 mm; 5µ) by gradient elution using mixtures of 0.02M ammonium acetate and methanol as the mobile phase. The analytes in the eluate were monitored at 250 nm. The retention times obtained for abacavir, lamivudine and zidovudine were 12.172, 1.884 and 4.378 min respectively. The calibration curves were linear over the range of 25-200 µg/mL for abacavir, 12.5-100 µg/mL for lamivudine and 25-200 µg/mL for zidovudine. The performance of the method was validated according to ICH guidelines. The method was found to be suitable for accurate determination of these drugs in tablet dosage forms without any interference from the excipients or endogenous substances. Key words: Abacavir, Lamivudine, Zidovudine, Determination, HPLC, Gradient elution.

The present work reports the study of different Lamivudine (LAM): excipient formulations, in order to determine the effect of the polymer substitution and type of diluents on the drug-release mechanism. Seven formulations were prepared using either HPMC K15M alone or in combination with Ethyl Cellulose (EC). Release kinetics was evaluated by using United States Pharmacopeia (USP)-22 type I dissolution apparatus. The tablets were tested for their drug content, weight variation, hardness, thickness, tensile strength, friability, swelling and release ratio. Polymers HPMC K15M was found not to be appropriate for the preparation of modified release LAM hydrophilic matrix tablets, while combination of HPMC K15M and EC showed to be advantageous. The analysis of the release profiles in the light of distinct kinetic models (zero-order, first-order, Higuchi and Korsmeyer–Peppas) led to the conclusion that the concentration of polymer did not influence the release mechanism of the drug. The mean dissolution time (MDT) and t50% was determined, the highest MDT and t50% value being obtained for HPMC and EC formulations. Moreover, the drug-release process was not found to be influenced by the type of diluents, either MCC or DCP. Key words: Lamivudine, HPMC, Ethyl Cellulose