Development and evaluation of verapamil resinates-loaded controlled release microcapsules using a binary polymer system in drug release rate modulation

The application of polystyrene-​divinylbenzene sulfonic acid-​based ion exchange resins as a carrier system for the sustained delivery of verapamil hydrochloride was primarily evaluated.  A large degree of variation in the loading efficiencies (drug loaded: 19.17-​48.86​%)​, was obsd. between the different drug-​resin complexes depending on resin type and drug​/resin ratio.  Upon comparing different carrier resins at drug​/resin ratio of 1:1, verapamil release in either 0.1 N HCl or phosphate buffer (pH 7.4) was in the order of Amberlite MB-​1 > Amberlite IRP-​69 (Na⁺) ≥ Amberlite IR-​120 (Na⁺) > Dowex-​50 W (Na⁺)​.  For further retardation of the drug release rate, microencapsulation of the strongly acidic cation exchange resin (Amberlite IR-​120 (Na⁺)​) loaded with verapamil hydrochloride (drug​/resin ratio of 1:1, resinate drug content: 48.86​%, core​/coat ratio of 1:2) was carried out by means of a modified emulsion-​solvent evapn. / extn. technique (ESE​/E) using different coating polymers, namely Et cellulose (EC)​, cellulose acetate phthalate (CAP)​, cellulose acetate butyrate (CAB) as well as CAB​/polystyrene (PS) binary polymer systems.  The effect of polymer type, polystyrene concn. and core​/coat ratio on the yield, size distribution as well as release characteristics and surface topog. of the microcapsules were investigated.  The results obtained revealed that polystyrene utilization as a complementary wall material at a particular compn. of 70:30 (​%) of CAB to PS was found to improve greatly the microcapsule yield, reduce the av. microcapsule size and modulate the in-​vitro release of the entrapped drug.  On the other hand, the entrapment efficiencies increased and the release rate decreased with increasing microcapsule size and​/or theor. drug loading of CAB​/PS (30​%) - microcapsules.  Kinetic assessment of the release data using different math. models showed that the drug release from CAB or CAB​/PS (7.5​%)​-​microcapsules (core​/coat ratio of 1:2) was found to be best explained by a Fickian-​diffusion kinetics (a diffusion-​controlled model for a planar matrix)​, whereas the calcd. exponential release exponents (n values) of the empirical equation (M_r/M_∞ = Ktⁿ) indicated that the release behavior of CAB​/PS (30​%) - microcapsules was a non-​Fickian-​diffusion kinetics, confirming that a diffusion / chain relaxation-​controlled release mechanism was operative.  Overall, this study demonstrated that the prepd. CAB​/PS microcapsules were capable of releasing their drug content gradually for an extended period of time, irresp. of variations in the pH of the gastrointestinal tract and exhibited slower release rates as compared with the com. sustained-​release product (Isoptin(SR) tablets)​.