Modified release from hydroxypropyl methylcellulose compression-coated tablets.
The goal of this study was to obtain flexible extended drug release profiles (e.g., sigmoidal, pulsatile, increasing/decreasing release rates with time) with hydroxypropyl methylcellulose (HPMC) compression-coated tablets. Drugs of varying solubility (carbamazepine, acetaminophen, propranolol HCl and chlorpheniramine maleate) were incorporated into the tablet core in order to evaluate the flexibility/limitations of the compression-coated system. The HPMC-compression-coating resulted in release profiles with a distinct lag time followed by different release phases primarily determined by the drug solubility. Carbamazepine, a water-insoluble drug, was released in a pulsatile fashion after a lag time only after erosion of the HPMC compression-coat, while the more soluble drugs were released in a sigmoidal fashion by diffusion through the gel prior to erosion. With carbamazepine, increasing the molecular weight of HPMC significantly increased the lag time because of the erosion-based release mechanism, while, in contrast, molecular weight did not affect the release of the more soluble drugs. The lag-time and the release rate could also be well controlled by varying the HPMC amount in and the thickness of the compression-coating. A pulsatile release could also be achieved for water-soluble drugs by introducing an enteric polymer coating between the drug core and the HPMC compression-coating. This novel concept of introducing an enteric subcoating eliminated drug diffusion through the gelled HPMC layer prior to its erosion. Incorporating drug in the compression-coating in addition to the tablet core in varying ratios resulted in release profiles with increasing, decreasing or constant release rates. In conclusion, a versatile single-unit delivery system for a wide range of drugs with great flexibility in release profiles was presented.
Rujivipat
Soravoot
S
College of Pharmacy, Freie Universität Berlin, Kelchstrasse 31, 12169 Berlin, Germany.
Bodmeier
Roland
R
D000284:Administration, Oral; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry*; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D008970:Molecular Weight; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D012995:Solubility; D013607:Tablets; D013608:Tablets, Enteric-Coated; D013997:Time Factors
D003692:Delayed-Action Preparations; D005079:Excipients; D004364:Pharmaceutical Preparations; D011108:Polymers; D013607:Tablets; D013608:Tablets, Enteric-Coated; D065347:Hypromellose Derivatives; D008747:Methylcellulose