Metoclopramide-OROS Dispersible Tablets Optimized Formula Bioavailability Study (original) (raw)
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OPTIMISED FORMULATION OF METOCLOPRAMIDE ORALLY DISINTEGRATING TABLET
Malaysian Journal of Pharmaceutical Sciences, 2014
Orally disintegrating tablet (ODT) was developed to solve the difficulty of swallowing conventional tablet for paediatric and geriatric patients. In administration of ODT, tablets are placed on the tongue in oral cavity and it will disintegrate rapidly in less than 60 seconds. The solid tapai extract (STE) has sweet taste, is rather sour and slightly soluble when it is put on the tongue. This is the reason why it has potential as a natural excipient in ODT. The objective of the study was to characterise STE as excipient and to use STE as excipient in the formulation of ODT by lyophilisation method. The ingredients were glutinous rice (Oryza sativa L. var. Glutinous) used to form tapai and the liquid extract of tapai which was used to make STE. STE was used as excipient by combining STE with dextrose and avicel. Metoclopramide HCl was used as a drug model. The design of formula used the simplex lattice design (SLD) model with a three components mixture: STE, dextrose and avicel as excipients. The parameters of lyophilised ODT (LODT) were hardness and friability, wetting time, disintegrating time and dissolution rate. The results showed STE can be used as filler and binder for LODT. STE could also function as disintegrant and formed porosity in the lyophilised method. Based on equation and contour plot of superimposed method, a formula consisting of STE (24.18 mg), dextrose (19.71 mg) and avicel (96.11 mg) was the optimum formula of LODT.
In Vitro-In Vivo Correlation Study of Metochlopramide-Orally Disintegrating Tablets
International Journal of PharmTech Research, 2016
Solid tapai extract had been applied as excipient in formulating orally disintegrating tablets (ODTs). Solid tapai extract was used as excipient by combining solid tapai extract with corn starch and avicel. The formula was designed using simplex lattice design method with three component mixture. The optimized formula was determined by in vitro and in vivo study. The objective of this pilot study was to discover in vitro and in vivo correlation of optimized metochlopramide-ODTs. The design of in vivo test designed by using six rabbits. The drug released in the plasma was measured by HPLC instrument using glacial acetic acid 1% in aquabidestilata and metanol-acetonitrile (1:3.7) with ratio 60:40. The result showed that in vitro test on pH 1.2 and 7.4 had correlation to in vivo test with coefficient correlation of 0.996 and 0.975.
International Journal of Applied Pharmaceutics, 2019
Objective: The purpose of present study was to formulate oral sustained release matrix tablet of metoclopramide hydrochloride and to evaluate the effect of varying concentrations of hydrophobic and hydrophilic polymers on drug release. Methods: Drug-excipients compatibility studies were carried out by using Fourier transform infrared spectroscopy (FTIR). The matrix tablets were prepared by direct compression technique using Xanthan gum and ethyl cellulose alone and in combination as release retardant. Dicalcium phosphate was used as diluent. The prepared matrix tablets were evaluated for their physicochemical parameters such as weight variation, hardness, friability, content uniformity and in vitro drug release studies were performed using USP-type II (paddle) dissolution apparatus. Results: Pre and post compression parameters were evaluated and all the parameters were found within the limit. The matrix tablets prepared with xanthan gum and combination of xanthan gum and ethyl cellulose were retarded the drug release upto 12 h. Ethyl cellulose alone could not control the drug release for 12 h. The Formulation with drug to xanthan gum (1:1.5), released 97.62 % of drug in 12 h. The kinetic treatment showed that the release of drug follows zero order kinetics (R 2 Conclusion: Matrix tablet is the simple, efficient and economic method to sustain the release of metoclopramide to prevent extrapyramidal side effects. =0.985). Korsmeyer and Peppas equation values of n were found to be in the range of 0.40-0.56, indicating that the drug release mechanism was diffusion.
World Journal of Pharmacy and Pharmaceutical Sciences, 2015
Orally disintegrating tablets were developed to solve the difficulty of swallowing the conventional tablet in pediatrics and geriatrics patients. In administration of orally disintegrating tablets, tablets are placed on the tongue in oral cavity and it will disintegrate rapidly in less than 60 second. Since solid tapai extract is slightly soluble when it puts on the tounge and has sweet taste, it has potential as a natural excipient in Article Received on
Pharmacokinetic Study of Optimized Metoclopramide HCl Formulations in Pakistani Volunteers
. Single centered crossover four phasic volunteer study was performed on eight healthy male volunteers after taking informed consent. Both market brand (Maxolon ®) and immediate release (IR) test formulations (F2) was given in a randomized manner in first phase with a washout period of two weeks. In second and third phase of intermediate (IntR) and slow release (SR) formulation blood samples were drawn with the same washout period. Plasma concentration of Metoclopramide HCl was determined by using the validated HPLC method. The time versus plasma drug concentration was then used for evaluating pharmacokinetic parameters including in vivo bioequivalence using Kinetica ® 4.4.1 PK/PD software. The mean maximum plasma concentration (C max) and peak time (T max) of F2 (immediate release) was found to be 35.933 ± 6.371 ng/mL and 0.783 ± 0.097 h, 22.006 ± 0.088 ng/mL and 0.976 ± 0.033 for intermediate release (F10) and 19.325 ± 1.306 ng/mL and 0.533 ± 0.082 h for slow release (F18) while t...
To examine the influence of environmental factors on the quality of a drug product over time, in order to recommend storage conditions and establish shelf life for the product, the accelerated stability studies for optimized formulations (Immediate Release- F2, Intermediate Release-F10 and Slow Release-F18), prepared for IVIVC Study, were carried out for a period of six months using ICH guidelines (at 40±2 oC and 75±5% RH). All the formulations were tested for disintegration test, % drug content and % drug release over the entire period of testing. Observations showed no degradation of the drug throughout the six months periods as % content uniformity of the three optimized immediate, intermediate and slow release formulations at one, three and six month was found within the limits. Moreover the results of drug release profiles at pH 1.2, 4.5, 6.8 and distilled water was also remained unaffected throughout the test period under elevated conditions when the trial formulations were compared with those stored in refrigerator. Shelf lives were calculated by software R Gui and were found to be 24, 14 and 20 months for IR (F2), IntR (F10) and SR (F18) formulations respectively. These stable novel optimized formulations will then be used for In Vitro In Vivo Correlation (IVIVC) studies of Metoclopramide HCl. No such stability studies of three formulations of Metoclopramide HCl with varying release rates are conducted before.
Journal of Applied Pharmaceutical Science, 2015
In recent years oral controlled delivery systems have gained increased importance and interest since it is necessary to improve the systemic absorption of the drugs and patient compliance. In addition, controlled delivery systems maintain uniform drug levels, reduce dose and hence dose related side effect, and increase the safety margin. The objective of present work was prepared sustained release solid dispersion of Metoclopramide HCl by solvent evaporation method. Several polymers like combination of Eudragit RSPO-Eudragit RLPO and Guargum-Egg albumin as synthetic and natural polymers respectively were used. Several parameters like Solubility, Partition coefficient, Drug content, Percent drug release, Bulk density, Tapped density and Carr's index were evaluated and all parameters were found to be in acceptable range. The results of XRD and SEM analysis were showed that the drug was converted into a solid dispersion. The In vivo studies were performed on Albino Wistar rats and various pharmacokinetics parameters were determined. The whole study was showed that the solid dispersion of Metoclopramide HCl sustained the release rate of drug for a prolong period of time at least 12 hrs and shows to increase the bioavailability and simultaneously decrease the dosing interval as well as dosing amount. The formulation minimizes the blood level oscillations, dose related adverse effects and cost and ultimately improve the patient compliance and drug efficiency.
Aims & Objectives: The present work deals with the modification of controlled release dosage form of poorly water soluble drug (Metoclopramide hydrochloride) in order to improve the bioavailability and to control drug release for a longer period of time by the aid of solid dispersion. Methods: Various binary combination of MET-solid dispersion was prepared with different carriers such as HPβCD, PVP K30 and PLX-188 by solvent evaporation technique and then the aqueous solubility, dissolution study and phase solubility study was performed. DSC analysis is performed to carry out for metoclopramide loaded solid dispersion, physical mixture & also for pure drug to analyze the crystalline and amorphous nature of compounds. Results and Discussion: The saturation solubility of Metoclopramide with various carriers at different pH was performed and found that in pH 5.5 (solubility is 5553.2µg/ml), pH 6.8 (3363.3µ/ml), pH 7.4 (1367.3µg/ml) at 37 o C. In dissolution study of solid dispersion (5:1) of different carriers in DDW, the Cumulative % dissolution is found in the order of PVP K30>PLX-Met>HPβCD-Met & in pH 7.4, in the order of PLX-Met>PVP K30>HPβCD-Met. DSC thermogram of Metoclopramide base showed a sharp endothermic peak at its melting point (147 o C) which exhibits in crystalline form complying with that of Metoclopramide hydrochloride form, melting point was found to be 85 0 C. In the ex-vivo study of several transdermal patches, patch C [SD of MET: HPβCD (1:5)] showed the controlled release and permeation of drug. Conclusion: Poor solubility of new chemical entities being a well known problem for past few decades despite the imbalance between significant research efforts & few successful marketed formulations, the solid dispersion proves to hold a key position among all the various formulation strategies to enhance the aqueous solubility & dissolution rate and thereby the bioavailability of poorly aqueous solubility of drug.
. The objective of the present study was to evaluate if two oral solid formulations of 10 mg of Metoclopramide HCl are bioequivalent after the administration of both reference and prepared formulations (newly designed and compressed) in fasting conditions, in healthy male Pakistani volunteers. The study used a randomized, single dose, single blind, controlled, cross-over, under fasting condition, design to compare the two products. The total number of volunteers enrolled in this study was 15, 8 of which were able to complete the study. A validated High Performance Liquid Chromatography method was used for the analysis of metoclopramide HCl in plasma. Both the market brand (Maxolon®) and test formulations were given in a randomized manner in first phase with a washout period of two weeks. No adverse events were observed in the study. The plasma drug concentration versus time was then used for evaluating pharmacokinetic parameters including in vivo bioequivalence using Kinetica® 4.4.1...
Formulation and Development of Fast Dissolving Tablet of Metoclopramide: An Anti-Emetic Drug
Journal of Biomedical and Pharmaceutical Research
Aim: The main of the study is to formulate and develop orally disintegrating fast dissolving tablet of Metoclopramide hydrochloride. Material & Methods: Before formulation and development of selected drug, the standard curve in buffer was prepared and absorbance at selected maxima was taken. Then two different disintegrating agents were selected and drug was mixed with disintegrating agents in different ratio. Various Preformulation parameters and evaluation of tablet i.e. disintegration time, dissolution time, friability, hardness, thickness were measured by standard procedure. Result & Discussion: The angle of repose for all the batches prepared. The values were found to be in the range of 30.46 to 36.45, which indicates good flow property for the powder blend according to the USP. The bulk density and tapped density for all the batches varied from 0.49 to 0.54 g/mL and 0.66 to 0.73, respectively. Carr’s index values were found to be in the range of 23.33 to 25.88, which is satisf...