Raloxifene HCl (RHCl) is known to be susceptible to oxidation and forms the corresponding N-oxide derivative as the primary degradation product. The purpose of this study was to evaluate the role of excipients on the generation of the N-oxide derivative from the corresponding RHCl-excipient binary mixtures. Binary mixtures of RHCl with crospovidone, povidone, magnesium stearate, Tween 80 and anhydrous lactose in drug: excipients ratio of 1 : 1 (crospovidone and povidone); 10 : 1 (Tween 80 and magnesium stearate) and 1 : 5 (anhydrous lactose) were prepared by both dry blending (trituration) and wet blending (to improve contact between drug and excipients). The prepared binary mixtures were then stored at 25, 40, 75 and 125°C and generation of the N-oxide derivative was monitored over six months using a validated HPLC method. Pure drug and excipients stored similarly acted as controls. Further, all the individual excipients (used as control) were monitored for peroxide impurity generation using an in-house colorimetric method. The results showed that N-oxide generation was observed from all binary mixtures and the amount of N-oxide derivative formed were always higher from the mixtures prepared by wet blending and the amount of N-oxide derivative formed was dependent on storage temperature. This study thus shows that the presence of peroxide in the excipient and its role in oxidative degradation of drug substance calls for monitoring of the peroxide impurity present in the excipients used for formulating of drug sensitive to oxidation as used herein.Key words raloxifene HCl; excipient; N-oxide-raloxifene; povidone; crospovidone Incompatibility between drugs and excipients can alter the stability and bioavailability of drugs, thus affecting its safety and efficacy. Study of drug-excipient compatibility is an important and integral process in the development of a stable dosage form. Many reports are available in the literature that has deliberated the importance of this issue and various methods of compatability testing have been discussed. [1][2][3][4][5] Raloxifene HCl (RHCl), is a selective estrogen receptor modulator shown to be effective in the prevention of osteoporosis, 6) which could be a potential substitute for long-term female hormone replacement therapy. Raloxifene is available as 60 mg tablet under the brand of Evista (Eli-Lilly) and contains 12.5% w/w RHCl, 5% povidone, 6% crospovidone and a combination of other excipients including anhydrous lactose, lactose monohydrate, Tween 80 and magnesium stearate. In an earlier published report, 7) it was disclosed that raloxifene forms a N-oxide derivative as a degradation product when the tablets were stored in sealed bottles and open containers at both 30°C/60% relative humidity (RH) and at 40°C/75% RH. Stability studies on binary mixtures of RHCl with primary excipients used in the tablet (Evista) were reported, 7) wherein the binary mixtures were stored at 125°C for a period of 31 d. The results showed that maximum amount of N-oxide derivative generation we...
A simple and rapid reverse phase high performance liquid chromatography (RP-HPLC) method was developed and validated for quantitative determination of rabeprazole in bulk drug samples and formulations. Rabeprazole was analyzed by using reverse phase LC-GC column (Inertsil ODS, 4.6 mm x 25 cm, 5 microns), with mobile phase consisting of methanol: water (78:22 v/v). The flow rate was set 1.0 mL/min and analysis was performed at wavelength 288 nm using Photo Diode Array (PDA) detector at ambient temperature. The method was validated and stability studies were conducted under different conditions. The retention time for rabeprazole was around 4.12 minutes. The calibration curves were linear (r≥0.9998) over a concentration range from 20.0 to 80.0 μg/mL. Limit of detection (LOD) and Limit of quantitation (LOQ) were 8 ng/mL and 24 ng/mL respectively. The developed method was successfully applied to estimate the amount of rabeprazole in tablet formulations.
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