FORMULATION AND IN VITRO EVALUATION OF MATRIX TABLETS OF METOCLOPRAMIDE HYDROCHLORIDE Original Article (original) (raw)
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Zero-order release profile of metoclopramide hydrochloride sublingual tablet formulation
Pharmaceutical Development and Technology, 2013
This report describes zero-order approximation for metoclopramide hydrochloride sublingual tablet formulation. Effects of type and concentration of excipients on release were investigated. Study revealed that highest rate of dissolution was attained with crosspovidone and decreased in the order crosspovidone > sodium starch glycolate > ac-di-sol. All formulations demonstrated flush release, except the one containing 10% crosspovidone where a lag time of 0.5 min. was depicted. Increasing the concentration of crosspovidone from 5 to 10% gave the same halflife, whereas kinetics of release changed to zero order. Differential scanning colorimetry and infrared spectroscopy did not reveal any sign of physical or chemical interaction between drug and crosspovidone. In order to study the alignment of polymeric network inside tablet matrix, scanning electron microscopy was performed on the tablet and its cross-section. Matrix with 10% crosspovidone showed higher density of interconnections extending to the interior of core enabling fast and constant release. Hence physicochemical characteristics of crosspovidone could be tailored by varying its concentration, in a way that provided a porous matrix with tight arrangement of polymeric chains, resembling to an assemblage of cylinders with constant apertures, from which zero-order release was approached.
LATIN AMERICAN JOURNAL OF PHARMACY
To select the suitable concentration level of controlled release polymer for the formulation of predefined extended release formulation based on the solubility behaviour of active substance, we have formulated and evaluated the extended release matrix tablets of two different antihypertensive drugs having different solubility profile by direct compression process. The selected antihypertensive drugs are metoprolol succinate of freely soluble category and propranolol hydrochloride of soluble category (solubility in terms of water). The selected drugs were formulated with various concentrations of selected highest viscosity grades of controlled release polymers viz. HPMC K200M & Polyox WSR 303 and evaluated for drug release profile. Dissolution methods were conducted using USP official methods. From the studies conducted it was found that drug solubility behavior also plays an important role in selection of controlled release polymer concentration for formulation of extended release formulation and observed that a higher concentration level of controlled release polymer is required for the formulation of freely soluble drug than soluble drug.
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.
Critical factors in the release of drugs from sustained release hydrophilic matrices
Journal of Controlled Release, 2011
Hydrophilic matrix systems are one of the most interesting drug delivery systems, and they are currently some of the most widely used to control the release rate of drugs. There are too much factors involved in drug release from hydrophilic matrix systems. The most important factors to be taken into account when developing a formulation based on hydrophilic matrices are the percentage, solubility and drug particle size; the type of polymer, the percentage incorporated, its degree of viscosity and the polymer particle size. Also important are the drug/polymer ratio and the amount of water entering the matrix. Other factors have been shown to be involved in the release of drugs, such as the percentage and mixtures of polymers and the dimensions of the matrix. The compression force is important among the formulation factors to the extent that it determines the amount of air trapped in the matrix. Knowledge of these factors involved in the release of the drugs is crucial for the optimal development of formulations based on hydrophilic systems.
PRINCIPLES OF DRUG RELEASE IN VARIOUS DOSAGE FORMS
Among various dosage forms parenteral dosage form stands in first place to exert its action in individuals and next to this in current day‟s aerosol and nasal dosage forms competent to parenteral route. Drug release may follow mixed mechanism of release; it may involve both diffusion and dissolution controlled processes. The drug release is function of excipients, in which the drug is embedded or covalently bound. type of excipients, their concentration, method of manufacturing, physico-chemical properties of drugs and excipients, design of dosage form (geometry), routes of administration, pharmacokinetic and physico-dynamic parameters of drug. Morphological characteristics such as porosity, tortuosity, surface area, and shape of the system. Hydrophilicity/hydrophobicity of the system, chemical interaction between drug and polymer, polymer characteristics such as glass transition temperature and molecular weight .It is not always correct to show the same type of release in all dosage forms with same excipients and is going to vary and depend upon release the all above parameters to subject optimization.
Colloids and surfaces. B, Biointerfaces, 2013
Theophylline extended release (ER) matrices containing hypromellose (hydroxypropyl methylcellulose (HPMC) E4M and K4M were evaluated in media with a pH range of 1.2-7.5, using an automated USP type III, Bio-Dis dissolution apparatus. The objectives of this study were to evaluate the effects of systematic agitation, ionic strength and pH on the release of theophylline from the gel forming hydrophilic polymeric matrices with different methoxyl substitution levels. Tribo-electric charging of hypromellose, theophylline and their formulated blends containing E4M and K4M grades has been characterised, along with quantitative observations of flow, compression behaviour and particle morphology. Agitations were studied at 5, 10, 15, 20, 25, 30 dips per minute (dpm) and also in the ascending and descending order in the dissolution vials. The ionic concentration strength of the media was also varied over a range of 0-0.4 M to simulate the gastrointestinal fed and fasted states and various physiological pH conditions. To study the effect of ionic strength on the hydrophilic matrices, agitation was set at 20 dpm. The charge results on individual components imply that the positively charged particles have coupled with the negatively charged particles to form a stable ordered mixture which is believed to result in a more homogeneous and stable system. The particle shape analysis showed the HPMC K4M polymer to have a more irregular morphology and a rougher surface texture in comparison to the HPMC E4M polymer, possibly a contributory factor to the gelation process. The results showed gelation occurred quicker for the K4M tablet matrices. Drug release increased with increased agitation. This was more pronounced for the E4M tablet matrices. The ionic strength also had more of an effect on the drug release from the E4M matrices. The experiments highlighted the resilience of the K4M matrices in comparison with the E4M matrices. The results thus show that despite similar viscosities of E4M and K4M, the methoxyl substitution makes a difference to their control of drug release and as such care and consideration should be given to the choice of polymer used for extended release. The use of systematic change of agitation method and ionic strength may indicate potential fed and fasted effects on drug release from hydrophilic matrices. address: a.nokhodchi@kent.ac.uk (A. Nokhodchi). contact with gastro-intestinal (GI) fluids, is eroded allowing drug release. This erosion is the dominant release mechanism for poorly soluble drugs . The other mechanistic approach is that the soluble portion of drug is released by diffusion through the gel layer . The non-ionic nature of HPMC means that when drug solubility is pH-independent, the matrices also exhibit pH-independent drug release profiles. Generally, the higher the solubility of the drug, the faster its release; this is due to a higher diffusional driving force.
The specific aim of this study was to prepare sustained release matrix tablets containing indapamide as a low dose and low water solubility model drug. The matrix formers were composed of blends of hydroxypropyl methylcellulose as a swellable polymer and methyl cellulose as an erodible polymer. The matrix tablets were prepared by the direct compression technique and they have shown robust and acceptable physical properties with a content uniformity within the acceptable limits. Lactose and microcrystalline cellulose were investigated as additives to these matrices in order to adjust and modulate the release of the drug from the matrices to achieve a release profile similar to that obtained from the reference commercial product, Natrilix ® . All matrix tablets prepared with these two additives have gave a release profile that is close to zero order kinetics, however, the matrix tablets prepared with lactose gave a release profile with closer resemblance to that of the reference product with a similarity factor (F2) of 86. This is attributed to the rapid water solubility of lactose which enhanced higher erosion of the tablets, and thus, higher dissolution and diffusion of the drug. Microcrystalline cellulose is a swellable polymer where it has resulted in delayed release of the drug with time as compared to the reference product. Investigation of the mechanism of release of the drug from the matrices indicated that erosion is the dominant mechanism of drug release from these matrices.
European Journal of Drug Metabolism and Pharmacokinetics, 2010
Oral dosage forms with controlled release exhibit various advantages over their immediate release counterparts, but they must be built adequately by dispersing the drug through the well-defined polymer matrix. This study is concerned with diffusion-controlled dosage forms to resolve the problems that appear: in vitro tests generally used for determining the kinetics of drug release do not take into account the nature of the drug. On the contrary, the plasma drug profiles obtained through in vivo tests strongly depend on the nature of the drug, through their typical pharmacokinetic parameters. Moreover, the effect of the stirring rate is difficult to evaluate. Following the demand from the FDA concerned with the in vitro/in vivo correlation, a numerical model was built so as to evaluate the plasma drug profile obtained with any drug delivered from a diffusion-controlled release dosage form. The results are expressed by connecting the half-life times of the drugs obtained either with bolus injection or with the dosage forms, for various values of the parameters of interest: the diffusivity of the matrix polymer and the size of the dosage form. Thus, these diagrams make it possible to promptly determine the characteristics of the dosage forms able to give the desired plasma drug profile for any drug. Of course, for each drug being defined by its pharmacokinetic parameters, the polymer matrix should be selected as a function of its diffusivity. Finally, the evaluation of the plasma drug profile is of effective help to determine quantitatively the effect of the intervariability of the patients as well as the effect of the patient’s noncompliance.
Metoclopramide hydrochloride is used to treat the gastrointestinal disorders. Frequent administration of metoclopramide hydrochloride can produce undesired side effects like decreased energy, diarrhea, dizziness, drowsiness, headache, nausea, vomiting, restlessness, malaise, trouble sleeping (insomnia). So, the aim of the present study was to formulate metoclopramide hydrochloride extended release matrix tablets by using different concentration of polymers (HPMC, Ethylcellulose, PVP, Eudragit E100) to minimize the dose size and dosing frequency of metoclopramide hydrochloride and study the in vitro release patterns of the drug. Metoclopramide hydrochloride matrix tablets were prepared by direct compression method by using various concentrations like 1%, 2% of HPMC, ethyl cellulose, PVP and Eudragit E-100 (1%, 1.5%, Eudragit E-100: Ethylcellulose). The prepared formulation batches were evaluated on the basis of weight variation, thickness, hardness, % of friability, % of drug content and in-vitro dissolution test. In-vitro dissolution test was done by using USP dissolution apparatus in phosphate buffer pH 7.2 as dissolution medium. The values of the evaluation were in acceptable range and the optimized formulas like B 5-B 8 containing the highest concentration of PVP, Ethylcellose, HPMC and Eudragit E-100 showed drug release within 12 hours, also