Abstract
The purpose of this research was to evaluate triple layer, donut-shaped tablets (TLDSTs) for extended release dosage forms. TLDSTs were prepared by layering 3 powders sequentially after pressing them with a punch. The core tablet consisted of enteric polymers, mainly hydroxypropyl methylcellulose acetate succinate, and the bottom and top layers were made of a water-insoluble polymer, ethyl cellulose. Drug release kinetics were dependent on the pH of the dissolution medium and the drug properties, such as solubility, salt forms of weak acid and weak base drugs, and drug loading. At a 10% drug loading level, all drugs, regardless of their type or solubility, yielded the same release profiles within an acceptable level of experimental error. As drug loading increased from 10% to 30%, the drug release rate of neutral drugs increased for all except sulfathiazole, which retained the same kinetics as at 10% loading. HCl salts of weak base drugs had much slower release rates than did those of neutral drugs (eg, theophylline) as drug loading increased. The release of labetalol HCl retarded as drug loading increased from 10% to 30%. On the other hand, Na salts of weak acid drugs had much higher release rates than did those of neutral drugs (eg, theophylline). Drug release kinetics were governed by the ionization/erosion process with slight drug diffusion, observing no perfect straight line. A mathematical expression for drug release kinetics (erosion-controlled system) of TLDSTs is presented. In summary, a TLDST is a good design to obtain zero-order or nearly zero-order release kinetics for a wide range of drug solubilities.
Keywords: Enteric polymers, donut-shaped tablets, triple layer tablets, erosion, diffusion
Full Text
The Full Text of this article is available as a PDF (268.9 KB).
References
- 1.Chien YW. Novel Drug Delivery Systems. New York, NY: Marcel Dekker; 1992. [Google Scholar]
- 2.Kydonieus A, editor. Treatise on Controlled Drug Delivery. New York, NY: Marcel Dekker; 1991. [Google Scholar]
- 3.Kim C. Controlled Release Dosage Form Design. Lancaster, PA: Technomic; 1999. [Google Scholar]
- 4.Roseman RW, Higuchi WI. Release of medroxyprogesterone acetate from a silicone polymer. J Pharm Sci. 1970;59:353–357. doi: 10.1002/jps.2600590317. [DOI] [PubMed] [Google Scholar]
- 5.Hsieh DS, Rhine WD, Langer R. Zero-order controlled-release polymer matrices for micro- and macromolecules. J Pharm Sci. 1983;72:17–22. doi: 10.1002/jps.2600720105. [DOI] [PubMed] [Google Scholar]
- 6.Lipper RA, Higuchi WI. Analysis of theoretical behavior of a proposed zero-order drug delivery system. J Pharm Sci. 1977;66:163–164. doi: 10.1002/jps.2600660207. [DOI] [PubMed] [Google Scholar]
- 7.Boettner WA, Aguiar AJ, Cardinal JR, et al. The moranted sustained release trilaminate: a device for the controlled ruminal delivery of morantel to cattle. J Control Release. 1988;8:23–28. doi: 10.1016/0168-3659(88)90096-X. [DOI] [Google Scholar]
- 8.Hansson AG, Giardino A, Cardinal JR, Curatolol W. Perforated coated tablets for controlled release of drugs at a constant rate. J Pharm Sci. 1988;77:322–326. doi: 10.1002/jps.2600770408. [DOI] [PubMed] [Google Scholar]
- 9.Kim C. Compressed donut-shaped tablets with zero-order release kinetics. Pharm Res. 1995;12:1045–1048. doi: 10.1023/A:1016218716951. [DOI] [PubMed] [Google Scholar]
- 10.Kim C. Release kinetics of coated, donut-shaped tablets for watersoluble drugs. Eur J Pharm Sci. 1999;7:237–242. doi: 10.1016/S0928-0987(98)00029-3. [DOI] [PubMed] [Google Scholar]
- 11.Ritger PL, Peppas NA. A simple equation for description of solute release, II: Fickian and anomalous release from swellable devices. J Control Release. 1987;5:37–43. doi: 10.1016/0168-3659(87)90035-6. [DOI] [PubMed] [Google Scholar]
- 12.Hilton TK, Deasy PB. Use of hydroxypropyl methylcellulose succinate in an enteric polymer matrix to design controlled-release tablets of amoxicillin trihydrate. J Pharm Sci. 1993;82:737–741. doi: 10.1002/jps.2600820713. [DOI] [PubMed] [Google Scholar]
- 13.Streubel A, Siepmann J, Peppas NA, Bodmeier R. Bimodal drug release achieved with multi-layer matrix tablets: transport mechanisms and device design. J Control Release. 2000;69:455–468. doi: 10.1016/S0168-3659(00)00334-5. [DOI] [PubMed] [Google Scholar]
- 14.Bari MM. Noncross-linked and cross-linked ampholytic polymers for controlled release carriers. Philadelphia, PA: Temple University; 2000. [Google Scholar]
- 15.Kim C. Effects of drug solubility, drug loading, and polymer molecular weight on drug release from Polyox® tablets. Drug Dev Ind Pharm. 1998;24:645–651. doi: 10.3109/03639049809082366. [DOI] [PubMed] [Google Scholar]
- 16.Kim C, Lee PI. Enhanced and retarded drug release from hydrophobic ionic beads. J Macromol Sci Pure Appl Chem. 1996;A33:1227–1238. [Google Scholar]
- 17.Lee PI. Diffusional release of a solute from a polymer matrix—approximate analytical solutions. J Memb Sci. 1980;7:255–275. doi: 10.1016/S0376-7388(00)80474-3. [DOI] [Google Scholar]
- 18.Lee PI. Interpretation of drug release kinetics from hydrogel matrices in terms of time-dependent diffusion coefficients. In: Lee PI, Good WR, editors. Controlled Release Technology: Pharmaceutical Applications. ACS Symp Series No 348. Washington, DC: American Chemical Society; 1987. pp. 71–83. [Google Scholar]