The data demonstrate that the new RP-HPLC method we have developed showed acceptable linearity, specificity, accuracy, precision and robustness in the concentration range of 4-80 µ g/ml for drotaverinehydrochloride and 5-100 µg/ml for nimesulide, as per the requirement of ICH guidelines. The method described is rapid since chromatographic run time is 7 min. In conclusion, the proposed method could be routinely used for the analysis of drotaverinehydrochloride and nimesulide in tablet dosage form.
A total of 10 tablets were weighed, their mean weight was determined and crushed in mortar. An amount of powder weight equivalent to 80 mg drotaverinehydrochloride, 250 mg ethamsylate, and 250 mg tranexamic acid was taken and transfer to 100 ml volumetric flask. The powder obtained was dissolved in mobile phase and sonicated for 20 min for complete extraction. The solution was made up to the volume with mobile phase. The solution was filtered through membrane filter. The stock solution was further diluted with mobile phase to get concentration of 80 µg/ml drotaverinehydrochloride, 250 µg/ml ethamsylate, and 250 µg/ml tranexamic acid.
I, Dr. SULTHANA NASEEMA BANU.NN. Solemnly declare that the dissertation “DROTAVERINEHYDROCHLORIDE VERSES HYOSCINE BUTYL BROMIDE IN AUGMENTATION OF LABOUR AMONG NULLIPAROUS WOMEN” is a bonafide work done by me at Government R.S.R.M Lying in Hospital, under supervision and guidance of Associate Prof. Dr. ARASI SRIVATHSAN, M.D., OG in Department of Obstetrics and Gynaecology, Government Stanley Medical College, Chennai. This thesis is submitted to The Tamil Nadu Dr.M.G.R. Medical University in partial fulfilment of the rules and regulations for the M.S. Degree examinations in Obstetrics and Gynaecology to be held in April 2016.
Drotaverinehydrochloride and aceclofenac are prescribed for the treatment of adult patients with muscular pain associated with spasm. This study describes a rapid, simple, precise and accurate RP-HPLC method for simultaneous estimation of drotaverinehydrochloride and aceclofenac in their combined tablet dosage form. The separation was achieved on a Phenomenex-Gemini (150mm x 4.6mm, 5 µm) column with an isocratic mixture of methanol, acetonitrile and water in the ratio of 60:30:10, pH adjusted to 3.0, at a flow rate of 1.0 ml/min and UV detection at 298.5 nm. The retention time for drotaverinehydrochloride and aceclofenac was 1.06 and 4.19 min respectively. The method was linear in the range of 8-40 µg/ml and 10- 50 µg/ml for drotaverinehydrochloride and aceclofenac respectively. The correlation coefficients were 0.9997 for drotaverinehydrochloride and 0.9995 for aceclofenac. The method was validated as per ICH guidelines and successfully applied for estimation of drotaverinehydrochloride and aceclofenac in commercially available tablet dosage form.
Randomized randomization was performed by computer- generated random code, created in blocks of ten at R. G. KAR G and O office in Kolkata. The code was used by employee of our college who were not part of the research team as a basis for sealing cards in consecutively numbered envelopes; the cards read either “Drotaverinehydrochloride” or “Valethamate bromide”. When a new participant was enrolled in the study, site staff opened the next envelope in the numbered series and the woman had received the treatment specified there in.
Two simple spectrophotometric methods have been developed for simultaneous estimation of drotaverinehydrochloride and aceclofenac from tablet dosage form. Method I is a simultaneous equation method (Vierodt’s method), wavelengths selected are 306.5 and 276 nm. Method II is the absorbance ratio method (Q-Analysis), which employs 298.5 nm as λ 1 and 276 nm as λ 2 (λmax of AF) for formation of equations. Both the methods were found to be linear between the range of 8-32 µg/ml for drotaverine and 10-40 µg/ml for aceclofenac. The accuracy and precision were determined and found to comply with ICH guidelines. Both the methods showed good reproducibility and recovery with % RSD in the desired range. The methods were found to be rapid, specific, precise and accurate and can be successfully applied for the routine analysis of drotaverine and aceclofenac in their combined tablet dosage form.
The authors are thankful to Alkem Pharmaceutical Pvt. Ltd., Mumbai and Aarti Drugs Pvt. Ltd., Mumbai, India and for providing gift samples of DrotaverineHydrochloride and Diclofenac Potassium, respectively. The authors are also thankful to Anchrom Laboratories for providing necessary facilities to carry out the research work.
monitored at 239 nm. The mobile phase consisted of acetonitrile - triethylamine – water (65:0.3:34.7 v/v/v), adjusted to pH 4.5 with 5% o-phosphoric acid. Under this conditions the retention time were of 4.14 and 5.87 minute respectively for drotaverinehydrochloride and nimesulide, indicating that the compounds were well separated. Total run was completed within eight minute. The method was validated for accuracy, precision, linearity, specificity and sensitivity as per ICH norms. The developed and validated method was successfully used for quantitative analysis of commercial formulation Nobel spas tablets. Validation study revealed that the method is specific, rapid, accurate, precise, reliable and reproducible.
Drotaverinehydrochloride (DRO) Chemically 1-[(3, 4-[diethoxyphenyl) methylene]-6,7- Diethoxy-1, 2,3,4-tetrahydroisoquinolene is an papaver analogue mainly used as an antispasmodic and smooth-muscle relaxant in pain associated with gastrointestinal colic, biliary colic and postsurgical spasms 1 . Aceclofenac, (ACE) chemically, 2-[(2’,6-dichlorophenyl) amino] phenylacetoxyacectic acid, is a phenylacetic acid derivative with potent analgesic and anti-inflammatory properties. It is official in Indian Pharmacopoeia 2 .
versus DrotaverineHydrochloride versus Hyoscine-N-Butylbromide for Duodenal Antimotility and ease of cannulation During Endoscopic Retrograde Cholangiopancreatography (ERCP)", is a bonafide work done by Dr.VADIVEL KUMARAN.S., Post-Graduate in Medical Gastroenterology, Madras Medical College, in partial fulfillment of the university rules and regulations for award of “D.M. IN MEDICAL GASTROENTEROLOGY” under my guidance and supervision during the academic year June 2013 to March 2014.
Simple, sensitive, selective, precise stability indicating chromatographic methods for determination of DrotaverineHydrochloride and Diclofenac Potassium from pharmaceutical tablets were developed and validated as per the ICH guidelines. A novel stability- indicating LC assay method was developed and validated for quantitative determination of Drotaverine and Diclofenac in bulk drugs and in pharmaceutical dosage form. An isocratic, reversed phase LC method was developed using an Qualisil BDS C8 column (250 mm x 4.6 mm, 5.0 µ particle size), using methanol: THF: acetate buffer (45:08:17 v/v) pH adjusted to 5.0 with acetic acid mobile phase, flow rate was 0.7 mL min -1 and column was maintained at 50 0 C. The detection was carried out at 292 nm and injection volume was 20 µL. The peak purity was checked with the photodiode array detector. DrotaverineHydrochloride and Diclofenac Potassium were subjected to acid, alkali and neutral hydrolysis, oxidation, photo degradation and dry heat and wet heat treatment. Degradation products were well separated from the analytes peaks. As the method could effectively separate the drug from its degradation products, it can be employed as stability-indicating one. The developed method was validated with respect to linearity, accuracy (recovery), precision, specificity and robustness.
The objective of the present study is to formulate and evaluate orally disintegrating taste masked drotaverinehydrochloride (HCl) tablets prepared by the melt granulation technique. Taste-masked drug—polymer melt granules of drotaverine HCl were prepared by using either compritol 888 ATO (compritol) or precirol ATO 5 (precirol) using varying drug-polymer ratios of 1:1, 1:2, 1:5, and 1:7. Prepared drug-polymer blends were evaluated for taste masking and the ratio of drug-polymer is optimized. The drug-polymer ratios 1:7 with compritol and 1:5 with precirol were optimized based on taste evaluation. The granules and tablets prepared with optimized drug-polymer ratio were evaluated for pre- and post-compression parameters. From all the prepared taste masked drotaverine HCl tablets, formulations CP9 and PF5 were optimized based on taste, mouthfeel, dissolution, and other oral disintegrating tablet (ODT) parameters. Formulations CP9 and PF5 showed the release of >50% drug in 5 minutes and 100% of the drug in 45 and 30 minutes, respectively. The optimized formulations were characterized by Fourier transformed infrared spectroscopy, differential scanning calorimetry, and XRD studies and found no incompatibility. The results demonstrated that the prepared drotaverine HCl ODT showed better taste masking meeting the parameters of ODT formulations PF5 > CP9. The present melt granulation technique can be effectively used for taste masking.
Conventional drug therapy requires periodic doses of therapeutic agents. These agents are formulated to produce maximum stability, activity and bioavailability. For most drugs, conventional methods of drug administration are effective, but some drugs are unstable or toxic and have narrow therapeutic ranges. These problems were overcome by sustained release systems. Gastro retentative drug delivery is one of the promising approch to retard the drug release and to retain the dosage form in stomach region. It also improve drug absorption, because of increased GRT and more time spent by the dosage form at its absorption site. Absorption of the DrotaverineHydrochloride is limited to upper part of the GI tract (stomach and upper part of small intestine) and bioavailability is 25-91%. DrotaverineHydrochloride has a rapid and direct action on the smooth muscle. It acts to correct cyclic AMP and Ca imbalance at the spastic site, thereby relieving smooth muscle spasm and pain. DrotaverineHydrochloride has a biological half-life of 7 to 12 hours so it requires three-times a day dosing. Hence attempt was made to develop DrotaverineHydrochloride floating matrix tablets to improve all characteristics . 7,8
This is to certify that the study entitled “Comparative Efficacy of DrotaverineHydrochloride and Valethamate Bromide on Cervical Dilatation in Active Labour” is the bonafide work done by Dr.B.Farhana Sulthana, at the Institute of Obstetrics and Gynaecology and Govt. Hospital for Women and children, attached to Madras Medical College, Chennai during the period of her Post Graduate study for MD Branch II Obstetrics and Gynaecology, from 2003 – 2006 under the guidance of Prof.Dr.Latha Jawahar, M.D. DGO.,
at floe rate 1 ml/min with column temperature 25º C. The method showed linearity over the range 40-180 µg/ml with correlation coefficient 0.9998.The drotaverinehydrochloride drug was subjected to acidic, alkaline, neutral, oxide, thermal and photolytic stress conditions. Drotaverine was found to be degrading significantly in alkaline, acid, oxide and photolytic stress conditions. Drotaverinehydrochloride was stable in neutral and thermal stress conditions. The developed method was validated according to ICH guidelines with respect to linearity, specificity, accurate, precise and robustness.
Phloroglucinol is one of spasmolytics, primarily used for gastrointestinal tract colic. The drug was extensively used during 1970s and early 1980s for augmentation of labor. There has been a resurge of interest in the subject. 18% incidence of Post-Partum Haemmorhage was reported due to uterine atony with the use Drotaverinehydrochloride. This incidence is statistically significant and limits the use of Drotaverine in labor. Although the number of patients with these complications were not large enough but still it is suggested that phloroglucinol can be used in patients with above mentioned complications with no toxic effects and a good outcome. Phloroglucinol shortens the duration of labor, is non toxic to both mother and foetus and does not cause uterine atony. It also has an analgesic action. As Spasmolytic, phloroglucinol have a definite role in obstetrics 2 .
Fadia H. Metwally (2008) compared the quantitative predictive abilities of the new and simple bivariate spectrophotometric method are compared with the results obtained by the use of multivariate calibration methods [the classical least squares (CLS), principle component regression (PCR) and partial least squares (PLS)], using the information contained in the absorption spectra of the appropriate solutions. Mixtures of the two drugs Nifuroxazide (NIF) and Drotaverinehydrochloride (DRO) were resolved by application of the bivariate method. The different chemometric approaches were applied also with previous optimization of the calibration matrix, as they are useful in simultaneous inclusion of many spectral wavelengths. 17
respectively, for drotaverine and aceclofenac . Pareek A. et al. (2010) evaluated the efficacy and safety of aceclofenac-drotaverine combination against aceclofenac alone in patients with primary dysmenorrhoea . Prasad R. K. et al. (2010) studied spectrophotometric Quantitative Estimation and Validation of Nimesulide and DrotaverineHydrochloride in Tablet Dosage form . Prasad P.D. et al. (2009) developed a reverse phase HPLC method for the quantitation of drotaverinehydrochloride and mefenamic acid in human plasma  . Parmar J. et al. (2009) described tablet Formulation Design and Manufacture of Oral Immediate Release Application . Rajmane S.V. et al. (2009) determined DrotaverineHydrochloride and Aceclofenac in tablet dosage form by Spectrophotometry. λ-max for Drotaverinehydrochloride and Aceclofenac is 242 nm and 273 nm respectively. Both the drugs obey Beer’s law in the concentration range 10-50 µg/ml .
Abstract: Purpose: Prolong labour contributes to increased perinatal and maternal morbidity. Inhibitory impulses in the form of spasm often impair the dilatation of cervix and prolong the duration of labour. This study was undertaken to compare the effect of Tramadol Hydrochloride And Drotavarine Hydrochloride on duration of labour and rate of cervical dilatation and compare it with control group. Method-300 patients were taken up for study. Of these 300 patients both primipara & multipara were included. In the multipara, only second para (OH=1001) were included to ensure comparability. 100 patients served as control. Majority of patients belong to age group 21-25 in all three groups. This is a Hospital based randomized study to evaluate the acceleration effect of Tramadol and Drotaverine on dilatation of cervix in both primigravida & multigravida with additional analgesic effect of Tramadol and compare it with control group,to note the time interval between injection of Tramadol and Drotaverine & delivery and compare it with control group,to determine deleterious effects if any of drugs affecting either fetus or mother in primi & multi patients with no high risk factors. Results - Both Tramadol and Drotaverine reduce the duration of first stage, less operative interference was required into two study groups in comparison to control group, in both primpara and multi para patients. Results of both drug are comparative.Among primiparous patients, two each of Tramadol and Drotaverine group had forcep delivery and two patients of Tramadol group had undergone lower segment cesarean section.Among multiparous patients, four patients of Drotaverine group delivered by lower segment cesarean section. Both the drugs had no significant action on the uterine contraction .Both the drug reduce the duration of active phase of labour and there who significant increase of rate of cervical dilatation in Tramadol and Drotaverine group compared to control group.Both the drugs had no significant effect on duration of second and third stage of labour. There was no significant difference in the APGAR score of babies delivered with the aid of Tramadol and Drotaverine as compared to control group.Both the drugs had minimal side effects and complications. Conclusion: It can be opined that Tramadol hydrochloride is a good cervical dilator and its effects is comparable to Drotaverinehydrochloride but due to its added analgesic effects, Tramadol can be preferred over Drotaverinehydrochloride and other cervical dilators for augmentation of labour.But further studies are required to have the data sufficient enough to establish the drug as better cervical dilator than Drotaverine.
In this study, a simple, rapid and reliable HPLC method was described for the assay of the ternary mixture of caffeine, dipyrone and drotaverinehydrochloride. To the best of our knowledge, there are no analytical reports describing the simultaneous determination of the three drugs in their combined dosage form. The analytes were successfully resolved and quantified using a RP-C18 column in a relatively short run time (less than 8 min). Consequently, the described method can be considered cost- and time-effective. Reliability was guaranteed by testing various validation parameters of the method and by successful application to laboratory-made tablets. Hence, it can be recommended for the routine quality control of the studied drugs either in bulk form or in their combined tablets dosage form.