Formulation of Sustained-Release Dosage Form of Verapamil Hydrochloride by Solid Dispersion Technique Using Eudragit RLPO or Kollidon®SR

Abstract

The release of verapamil hydrochloride from tablets with Eudragit RLPO or Kollidon SR with different drug-to-polymer ratios were investigated with a view to develop twice-daily sustained-release dosage form by solid dispersion (SD) technique. The SDs containing Eudragit RLPO or Kollidon SR at drug-polymer ratios of 1:1, 1:2, and 1:3 with verapamil hydrochloride were developed using solvent evaporation technique. The physical mixtures of drug and both polymers were prepared by using simple mixing technique at the same ratio as solid dispersion. The physicochemical properties of solid dispersion were evaluated by using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and differential scanning calorimetry (DSC). The study of DSC, XRD, and FTIR could not show significant interaction between verapamil HCl and Kollidon SR or Eudragit RLPO. The solid dispersions or physical mixtures were compressed to tablets. The tablets were prepared with solid dispersions containing Eudragit RLPO or Kollidon SR, with all the official requirements of tablet dosage forms fulfilled. Tablets prepared were evaluated for the release of verapamil hydrochloride over a period of 12 h in pH 6.8 phosphate buffer using US Pharmacopoeia type II dissolution apparatus. The in vitro drug release study revealed that the tablet containing Eudragit has extended the release rate for 12 h whereas the tablet containing Kollidon SR at the same concentration has extended the release rate up to 8 h. The in vitro release profile and the mathematical models indicate that release of verapamil hydrochloride can be effectively controlled from a tablet containing solid dispersions of Eudragit RLPO. The reduction of size fraction of the SD system from 200-250 to 75-125 microm had a great effect on the drug release.

Formulation and in-vitro bioequivalence evaluation of verapamil hydrochloride matrix tablets with Calan R

“…These models were utilized in the prediction of drug behavior and release kinetics (Sahoo et al, 2009). Similarity (f2) and difference (f1) factors were also calculated by the following equations Gohel et al, 2002).…”

“…However, it undergoes extensive first pass metabolism which results in only 20% bioavailability. Keeping in view these facts, formulating a controlled release dosage form for Verapamil Hydrochloride is gaining interest to increase the therapeutic efficacy and patient compliance (Sahoo et al, 2009). Matrix tablets can be formulated by using natural polymers by direct compression of the mixture of active ingredient, retardant material and additives.…”

Quince Seeds Biopolymer: Extraction, Drying Methods and Evaluation

“…It is medically used as a demulcent and for the treatment of asthma and coughing, while it may also be used as a flavoring agent or preservative (3). Mucilage are biopolymers most commonly used as adjuvants in the manufacturing of different pharmaceutical products and include binding, thickening, stabilizing, humidifying (4,5), disintegrating (6), suspending (7), emulsifying (8), and sustaining properties (9), at different proportions in many pharmaceutical dosage forms. Natural mucilage are preferred over semi-synthetic and synthetic materials due to their non-toxic, low cost, free availability, emollient and nonirritating nature (10).…”

Influence of magnesium stearate on the physicochemical and pharmacodynamic characteristics of insulin-loaded Eudragit entrapped mucoadhesive microspheres

“…Further advantages of microspheres include effective protection of encapsulated drugs against degradation, increased drug solubility, reduced adverse or toxic effects, site-specific drug delivery and controlled drug release (Singh et al, 2010). Microspheres based on Eudragits Õ have been explored for various drug delivery applications (Agyilirah & Banker, 2000;Haznedar & Dortunc, 2004;Sahoo et al, 2009;Apurba et al, 2009;Kishori et al, 2013), including insulin delivery (Kinesh et al, 2010;Singh et al, 2010b;Zhang et al, 2011;Cárdenas-Bailón et al, 2013). Eudragit Õ polymers are more favored in the formulation of pH-sensitive drug molecules.…”

“…The ammonium groups are present as salts and make the polymers permeable (Haznedar & Dortunc, 2004). Eudragit Õ RL is a low water permeable, cationic, non-biodegradable polymer commonly used for the preparation of controlled-release dosage forms, and represents a good material for the dispersion of drugs (Sahoo et al, 2009). It is composed of poly (ethylacrylatemethylmethacrylate-trimethylammonioethyl methacrylate chloride) copolymers with ratios 1:2:0.1 containing a low level of quaternary ammonium groups in 4.5-6.6%.…”