Pregabalin

Neuropathic pain is intense in nature and difficult to maintain. The main aim of this study is to provide maximum relief from pain.  The objective was to prepare bilayer tablet comprising  of pregabalin and methylcobalamin for effective treatment of neuropathic pain. Methylcobalamin was formulated as immediate release (IR) layer using super-disintegrant sodium starch glycolate (SSG) whereas pregabalin was formulated as sustained release (SR) layer using polymers hydroxypropyl methyl cellulose (HPMCK4M, K100M)  to deliver the drug at sustained manner effective for the treatment of neuropathic pain. The SR layer of pregabalin is prepared by wet granulation method and IR layer of methylcobalamin is prepared by direct compression method. Tablet blends were evaluated through various pre-compression and post-compression tests. Super disintegrant, SSG at 20% concentration produced excellent results for immediate release of methylcobalamin to exert its action and other additional beneficial effects. The K100M and K4M grade of HPMC produced excellent SR efficiency. Optimum formulation released methylcobalamin and pregabalin at 98.92%  in 45 min and 97.81% in 12 h from respective layers. Pre-compression and post-compression parameters of optimized IR layer comprising Methylcobalamin and SR layer comprising pregabalin exhibit satisfactory results. Bilayer tablet of Methylcobalamin and pregabalin prove to be effective as a combination therapy for the treatment of neuropathic pain by sequential release of the drug.

To method develop and validate simple, rapid, cost effective, linear, accurate, precise and economical for the simultaneous estimation of Pregabalin and Methylcobalamin in bulk and tablet dosage form by using UV-Spectrophotometry. The drug obeyed the Beer’s law and showed good correlation of concentration with absorption which reflect in linearity. The UV-Spectroscopic method was developed for estimation of Pregabalin and Methylcobalamin in bulk and tablet dosage form and also validated as per ICH guidelines. The method based on measurement of absorbance at two wavelengths 222 nm (λmax of Pregabalin) and 219 nm (λmax of Methylcobalamin) in Ethanol and distilled water. Linearity graph of Pregabalin and Methylcobalamin were found to be linear in the concentration ranges of 30-150 μg/ml and 0.6-3 μg/ml, respectively, with their correlation coefficient values (R2) 0.999. The low %RSD values indicate method to be accurate and precise. The % recovery of tablets found to be in range of 97-102% and other validation parameter were found to be within the limits as per ICH guidelines.

The present work deals with the formulation and evaluation of floating tablets of Pregabalin using Thermoplastic granulation or Melt granulation technology1. Thermoplastic granulation is a process by which granules are obtained through the addition of a meltable binder which melts during the process. This technology is used to modify or control drug release of highly water soluble drugs using hydrophobic meltable binders as done in this present work. Pregabalin is a primary medication for epilepsy, neuropathic pain, and fibromyalgia was selected for this work. The primary objective was to formulate and evaluate floating tablets of the Pregabalin by using different meltable binders like stearic acid, bees wax, carnauba wax along with other excipients such as HPMC K4M (3000cps), ethyl cellulose, sodium bicarbonate in various proportions by employing thermoplastic granulation method Pregabalin has absorption window in the upper region of small intestine hence it is suitable candidate for floating systems. FTIR spectroscopic studies suggested that the drug is compatible with all excipients used in this formulation. The formulations were evaluated for the pre-compressional and post-compressional parameters. The floating tablets were evaluated for the floating ability and also percentage drug release by using 0.1 N HCl as dissolution medium. The formulation F10 with stearic acid as the meltable binder along with ethyl cellulose had floating ability of not less than 12 hours with a good drug release profile. The optimized formulation followed Higuchi mechanism which shows both diffusion and erosion.

A simple, rapid reverse phase high performance liquid chromatographic method (RP- HPLC) has been developed and validated for simultaneous estimation of Aceclofenac and Pregabalin in tablet dosage form. Chromatographic separation was achieved C-18 (250 mm × 4.6 mm, 5.0μ) as stationary phase and mobile phase containing phosphate (pH adjusted to 5.0 ± 0.05 using NaOH.) Buffer: Acetonitrile (30:70 v/v) at flow rate of 1 ml/min using UV detection at 210 nm. The retention time for Aceclofenac and Pregabalin was found to be 3.177 and 5.530 min respectively. The method was validated as per International Conference on Harmonization guideline and successfully used for the quantitative analysis of commercially available tablet. The calibration curve was linear over the concentration range of 20-60μg/ml for Aceclofenac and 15-45μg/ml for Pregabalin.. Lower values of Limit of Detection (0.60μg/ml for Aceclofenac and 0.88μg/ml for Pregabalin) and Limit of Quantification (1.84μg/ml for Aceclofenac and 2.68μg/ml for Pregabalin ) indicated good sensitivity of the method. The method was validate with respect to linearity, robustness, precision and accuracy and was successfully applied for the simultaneous determination of aceclofenac and pregabalin from the combined dosage formulation. The percent amount for both the drugs were found to be within limits in the tablet dosage form for both the methods.