Chronopharmaceutical drug delivery from a pulsatile capsule device based on programmable erosion.
We report the development of a chronopharmaceutical capsule drug delivery system capable of releasing drug after pre-determined time delays. The drug formulation is sealed inside the insoluble capsule body by an erodible tablet (ET). The release time is determined by ET erosion rate and increases as the content of an insoluble excipient (dibasic calcium phosphate) and of gel-forming excipient (hydroxypropylmethylcellulose; HPMC) increases. The time-delayed release of a model drug (propranolol HCI) was investigated by dissolution testing (USP XXIII paddle method). Both composition and weight of ET influence the time of drug release. Moreover it was found that drug release was controlled by the quantity of HPMC, irrespective of lactose content within the tablet weight range 80-160 mg, when above a threshold concentration of 20% HPMC. Programmable pulsatile release has been achieved from a capsule device over a 2-12-h period, consistent with the demands of chronotherapeutic drug delivery. The time of drug release can be controlled by manipulation of tablet formulation.
Ross
A C
AC
Department of Pharmaceutical Sciences, University of Strathclyde, Glasgow, UK.
MacRae
R J
RJ
Walther
M
M
Stevens
H N
HN
D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D007785:Lactose / Q000031:analogs & derivatives*; D008747:Methylcellulose / Q000031:analogs & derivatives*; D010078:Oxazines; D011433:Propranolol / Q000008:administration & dosage; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods*
D003692:Delayed-Action Preparations; D010078:Oxazines; D013607:Tablets; D008747:Methylcellulose; C071191:MK 458; D011433:Propranolol; D007785:Lactose