title: Erosion characteristics of an erodible tablet incorporated in a time-delayed capsule device.
abstract: A time-delayed oral drug delivery device was investigated in which an erodible tablet (ET), sealing the mouth of an insoluble capsule, controlled the lag-time prior to drug release. The time-delayed capsule (TDC) lag-time may be altered by manipulation of the excipients used in the preparation of the ET. Erosion rates and drug release profiles from TDCs were investigated with four different excipient admixtures with lactose: calcium sulphate dihydrate (CSD), dicalcium phosphate (DCP), hydroxypropylmethyl cellulose (HPMC; Methocel K100LV grade) and silicified microcrystalline cellulose (SMCC; Prosolv 90 grade). Additionally, the compressibility of different insoluble coated capsules was tested at different moisture levels to determine their overall integrity and suitability for oral delivery. Erosion rates of CSD, DCP, and SMCC displayed a nonlinear relationship to their concentration, while HPMC indicated rapid first-order erosion followed by zero-order erosion, the onset of which was dependent on the HPMC concentration. Capsule integrity was confirmed to be most suitable for oral delivery when the insoluble ethyl cellulose coat was applied to a hard gelatin capsule using an organic spray coating process. T50% drug release times varied between 245 (+/-33.4) and 393 (+/-40.8) minutes for 8% and 20% DCP, respectively, T50% release times of 91 (+/-22.1) and 167 (+/-34.6) were observed for 8% and 20% CSD; both formulations showed incidence of premature drug release. The SMCC formulations showed high variability due to lamination effects. The HPMC formulations had T50% release times of 69 (+/-13.9), 213 (+/-25.4), and 325 (+/-30.3) minutes for 15%, 24%, and 30% HPMC concentrations respectively, with no premature drug release. In conclusion, HPMC showed the highest reproducibility for a range of time-delayed drug release from the assembled capsule formulation. The method of capsule coating was confirmed to be important by investigation of the overall capsule integrity at elevated humidity levels. The erosion characteristics of ETs containing HPMC may be described by gravimetric loss. The novel time-delayed capsule device presented in this study may be assembled to include an erodible tablet with a known concentration of HPMC. A variety of suitable drugs for targeted chronopharmaceutical therapy can be incorporated into such a device, ultimately improving drug efficacy and patient compliance, and reducing harmful side effects.
authors.affiliation: College of Pharmacy, University of Texas at Austin, TX 78712-0126, USA. jtmcconville@mail.utexas.edu
authors.forename: Jason T
authors.initials: JT
authors.lastname: McConville
authors.forename: Alistair C
authors.initials: AC
authors.lastname: Ross
authors.forename: Alastair J
authors.initials: AJ
authors.lastname: Florence
authors.forename: Howard N E
authors.initials: HN
authors.lastname: Stevens
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage; D002130:Calcium Phosphates; D002133:Calcium Sulfate; D002214:Capsules; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D005079:Excipients; D007785:Lactose / Q000031:analogs & derivatives*; D008747:Methylcellulose / Q000031:analogs & derivatives*; D010078:Oxazines; D011433:Propranolol / Q000008:administration & dosage; D012995:Solubility; D013607:Tablets
chemical_list: D000319:Adrenergic beta-Antagonists; D002130:Calcium Phosphates; D002214:Capsules; D003692:Delayed-Action Preparations; D005079:Excipients; D010078:Oxazines; D013607:Tablets; D008747:Methylcellulose; C071191:MK 458; D011433:Propranolol; D007785:Lactose; D002133:Calcium Sulfate