Semisolid matrix-filled hard gelatin capsules for rapid dissolution of amlodipine besilate: Development and assessment

The objective of the study was to prepare semisolid capsules (SSCs) of poorly water-soluble drug amlodipine besilate (AB) using a combination of technologies involving solid dispersion (SD) preparation and converting it into semisolid matrix filled in hard gelatin capsules (termed as SSCs) with the aim of reducing lag time in drug release and to improve the dissolution rate. AB is used for its anti-arrhythmic, anti-anginal, and anti-hypertensive activity. These are the emergency activities which should be treated as fast as possible like in the case of angina attack (heart attack). Any lag time that is generated due to its poor dissolution can add on in this emergency and that can be avoided by developing a readily dissolvable formulation: SDs of AB. SD of AB was prepared by fusion method using varying combinations of Poloxamer 407 and Plasdone S630. A total of nine batches (SD1–SD9) were characterized for the in vitro dissolution behavior in phosphate buffer pH7.4. SD8 with 95.8% cumulative drug release in 60 min, t(50%) = 4.1 min and DE(30 Min) = 84.2% were selected for the development of the semisolid matrix. Differential scanning calorimetry of SD8 revealed molecular dispersion of AB and Plasdone S630 in Poloxamer 407. SD8 was then formulated as SSCs using gelucire 44/14 and PEG 400 as semisolid components and PEG 6000 as a suspending agent to achieve the reduction in lag time for drug release. A total of seven SSC formulations were prepared and evaluated for drug release. Formulation of SSC4 showed maximum cumulative drug release (CDR) of 98.9% within 20 min that was almost a threefold reduction in the time required to achieve similar CDR by SD of AB. Thus, SSCs present an excellent approach to enhance the dissolution as well as to reduce the lag time of dissolution for poor water-soluble drugs especially to those therapeutic classes that are intended for faster onset of action.