Effects of polymer type, polymer: direct tabletting agent ratio and tabletting method on verapamil hydrochloride extended release from hydroxypropylmethylcellulose matrix tablets: polimer tipinin, pol (original) (raw)
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Comparative release profile of sustained release matrix tablets of verapamil HCl
International Journal of Pharmaceutical Investigation, 2013
Introduction: Verapamil hydrochloride (VH) is a calcium channel blocking agent used in the treatment of hypertension, cardiac arrhythmia and angina pectoris. The short half-life and high frequency of administration of VH makes it a suitable candidate for designing sustained drug delivery system. The aim of the present investigation was to develop a sustained release matrix tablet of verapamil hydrochloride (VH) using ethyl cellulose, methyl cellulose, Eudragit RS 100, hydroxypropyl methylcellulose and carboxymethyl cellulose and to evaluate the drug release kinetics. Materials and Methods: In order to achieve the required sustained release profile, the tablets were prepared by a wet granulation method using avicel PH 101 and magnesium stearate as binder and lubricant, respectively. Results: The formulated tablets were characterized for pre-compression and post-compression parameters and they were in the acceptable limits. The drug release data obtained after an in vitro dissolution study was fitted to various release kinetic models in order to evaluate the release mechanism and kinetics. The criterion for selecting the best fit model was linearity (coefficient of correlation). Drug release mechanism was found to follow a complex mixture of diffusion, swelling and erosion. Furthermore, to minimize the initial burst drug release, batches were coated by using Eudragit RS100 polymer. After coating the tablets, a better release profile of the formulated tablets was expected and the release rate of the drug was compared with the marketed SR tablet of VH. Conclusion: The dosage form holds the potential to control the release rate of drug and extend the duration of action of a drug.
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.
Asian Journal of Pharmaceutics, 2011
V erapamil hydrochloride was formulated as oral-controlled release matrix tablets using hydrophilic polymer such as hydroxypropyl methylcellulose K 15 M (HPMC 15 M) along with electrolytes. In this work a new attempt was made for in situ interactions between drug and electrolytes were devised to control the release of highly water soluble drugs from oral hydrophilic monolithic systems. Electrolytes such as aluminum hydroxide and sodium carbonate were used at different concentrations in various formulations, while drug and polymer concentrations were maintained constantly at 1:2 ratios in all the formulations. These electrolytes were used to monitor matrix swelling and gel properties. Electrolytes at higher concentrations exhibited greater inhibition in drug release from the matrix and low concentrations were accounted for controlled release of the drug. The results indicated that the drug released at a controlled rate were due to differential swelling rate and matrix stiffening, and provides a uniform gel layer. These findings indicated that the swelling and gel formation in the presence of ionizable species within the hydrophilic matrices provide an attractive alternative for controlled drug delivery from a simple monolithic system. Accelerated stability studies were carried out as per ICH guidelines for some selected formulations, which indicated that these formulations were stable at accelerated storage conditions.
2019
Objective: The mechanism of drug release is controlled by polymer swelling and erosion, and drug dissolution/diffusion. This study aimed to examine the effects of 3 natural polymers, i. e. , xanthan gum (XG) , pectin (P) , and okra mucilage (OM) on the release kinetics of propranolol hydrochloride (PRH) in pH 6. 8 phosphate buffer from hydrophilic matrices. Methods: Each formulations contained 80 mg PRH at a mass fraction (mf) of 0. 22. For formulas using P or OM, each polymer was used at the mf of 0. 30, 0. 45, 0.60 and 0.75; while those using XG, at the mf of 0.15, 0.30, 0.45 and 0.60. Microcrystalline cellulose (MCC) was added to make the the constant tablet weight of 360 mg. All tablets were prepared by direct compaction, and USP dissolution apparatus I was used to study the drug release in pH 6. 8 phosphate buffer from matrices within 24 h. Results: According to Higuchi equation, the results showed that the amount of drug released from matrices of all formulas depended upon the square root of time. From Higuchi equation, a retardability for drug release of any polymers depended on an ability to decrease both the kinetic rate constant (k), and natural convection (Q 0). An analysis of variance (ANOVA, P-value < 0.01) was performed for various k and Q 0. For k, the results showed that: (i) when XG with mf of 0.15-0. 60 and P with mf of 0. 30-0. 75 were used, the increased mf of polymer could decrease k significantly, and (ii) when OM with mf of 0.30-0.75 were used, the increased mf could only decrease Q 0 remarkably, but could not significantly decrease k. For Q 0 , the results indicated that the efficacy to lower Q 0 could be ranked as that of XG > OM >> P. Based on the ability to lower k and Q 0 , the sustainability of polymers for drug release could be ranked as that of XG > OM >> P. Conclusion: Various drug release models were applied to drug release data in order to explain the release mechanisms and kinetics of propranolol hydrochloride.
Development of Hydrophobic Carriers based tablets for Sustained Release of Verapamil
The main aim of the study is to formulate sustained release matrix tablets of verapamil hydrochloride using hydrophobic carriers or meltable binders like stearic acid, carnauba wax and bees wax by melt granulation technique. The influence of a hydrophilic polymer like polyethylene glycol (PEG) was studied on the waxy matrices. Two grades of PEG (4000 and 6000) were used in the preparations. The granules were prepared and compressed into tablets and they are evaluated for their physicochemical properties and in vitro dissolution studies were done. The IR spectral analysis revealed that there are no interactions between drug and the polymers and are compatible with other. The release data were subjected to various release kinetic models and also compared with those of a commercial brand. The tablets prepared fulfilled all the official requirements according to the pharmacopeia. From the dissolution studies it was observed that carnauba wax acts a good retardant (more than 16 h). Among the two grades of PEG used 4000 and 6000, PEG 6000 increases the drug release to a greater extent than PEG 4000. It was concluded that hydrophobic carriers which act as very good retardants of the drug and also PEG can be used as a channeling agent in waxy matrices to regulate the release of the drug.
International Journal of Pharmaceutics, 2015
The aim of this work was to evaluate and optimize formulation of three-layer matrix tablets based on xanthan gum (XG) and sodium alginate for chronotherapeutic pH-independent release of verapamil HCl (VH). Artificial neural networks (ANN) were applied in the optimization and compared with multiple linear regression (MLR). A face-centered central composite experimental design was employed with three factors (mass fraction of VH in intermediate layer, X 1 , and of XG in matrix former of intermediate and outer layers, X 2 and X 3). The prepared tablets were tested for in vitro release in 0.1 N HCl and phosphate buffer (pH 7.5), tensile strength and friability. Furthermore, swelling observation and release modeling to Weibull function and power law equation of Peppas were employed to help further understanding of release behavior and mechanism. The releases (%) in phosphate buffer (pH 7.5) at 6, 12 and 24 h were selected as responses to depict the mode of release and similarity factor (f 2), between release profiles in 0.1 N HCl and pH 7.5 during the first 8 h, as response of pH-independence. A desirability function combining the four responses was constructed and overall desirability values were used for the ANN and MLR modeling. Five additional checkpoint formulations, within the experimental domain, were used to validate the external predictability of the models. The constructed ANN model fitted better to the overall desirability than the MLR model (R = 0.838 vs. 0.670, for the additional checkpoint formulations) and therefore, was used for prediction of formulation with optimal in vitro drug release.
Drug Transport Mechanisms from Carbopol/Eudragit Verapamil Sustained-Release Tablets
Dissolution Technologies, 2011
The objectives of this study were to compare dissolution profiles of a verapamil (VRP) formulation manufactured inhouse and Isoptin SR using USP Apparatus 2 and 3 and to elucidate drug release kinetics of these dosage forms. Eudragit NE 30D (ethyl acrylate-methyl methacrylate copolymer in a 2:1 ratio) aqueous dispersion was used as a granulating binder for the manufacture of VRP mini-matrix sustained-release tablets. The wet granulation process was performed to prepare free-flowing granules that were blended with Carbopol. The tablets were manufactured using a single-punch press by compression of the granules with magnesium stearate as a lubricant. Drug release was determined in phosphate buffer solution using USP Apparatus 2 and 3. Dissolution data were fitted to zero-and first-order models; in addition, the kinetic data were determined by evaluation of Higuchi release kinetics. The mechanism of drug release was established using the Korsmeyer-Peppas model. In general, all tablets showed high mechanical resistance with less than 1% friability. There was no significant difference between the dissolution profiles of the formulation manufactured in-house and the commercially available product. The release mechanism of the formulated and marketed products was controlled by anomalous non-Fickian diffusion. VRP release was prolonged for 12 h indicating the usefulness of the formulation as a twice-daily dosage form. The mechanism of drug release for the dosage forms was unaffected by the choice of apparatus.
Journal of Pharmaceutical Sciences, 2008
This investigation is aimed at characterization of the mode of release from two different substitution types of HPMC and the effect of chemical structure of drugs using the QSPR (Quantitative -Structure-Property Relationship) technique. To this end, release profiles of HPMC matrices of several drugs containing the same formulation and compressed at a constant pressure were studied. QSPR method was used to establish statistically significant relationships between release parameters and the structural descriptors. Structural descriptors consisted of molecular mechanical, quantum mechanical and graph-theoretical parameters, as well as the partition coefficient and the aqueous solubility of the drugs. The results showed that the most important factors determining the release profile from both HPMC K4M and HPMC E4M matrices were the aqueous solubility of drugs (which could be substituted efficiently by dipole moment) and the size of the drug molecules. Comparison of drug release from matrices prepared using the two grades of HPMC showed very distinct differences for some drugs, as evaluated by the similarity factor. The results indicated that the source of the difference could be sought in the drug properties (as exemplified by the aqueous solubility and surface area) as well as the rate of erosion (that depends mainly on the polymer type). ß