A novel three-layered tablet consisting of a water-soluble mid-layer and two barrier layers with swellable polymers was investigated to develop a preferable once-a-day formulation containing terazosin HCl as a hydrophilic model drug. When the tablet was exposed to a release medium, the medium quickly permeated to the mid-layer and the two barrier layers swelled surrounding the mid-layer rapidly. It facilitated the tablet to absorb a lot of water compared with monolithic matrix. Moreover, formation of a lot of pores in the tablet during dissolution could be observed, suggesting significant water absorption in the inner matrix and swollen polymers of the tablet. Barrier layers influenced drug release profiles significantly, potentially due to differences in viscosity after swelling that produce different diffusion coefficients and mechanical strength. The drug in the mid-layer showed the sigmoid type of release pattern because a period of time might be needed to release the drug from the mid-layer through the barrier layers, but the drug in barrier layers showed the typical release pattern of monolithic matrix. As the amount of water-soluble excipient in the mid-layer increased, the degree of swelling also increased, suggesting that its amount in the layer may affect the overall swelling properties of the tablet. It was also shown that more hydrophilic mid-layer caused faster erosion rate, which was related to the results of swelling property. The three-layered tablets showed more consistent release kinetics than the matrix tablets. These results can give good information for the development of sustained drug delivery systems, especially once-a-day administration.
Regular ArticleA novel three-layered tablet technology consisting of an inner immediate release layer and two extended release barrier layers with swellable polymers has been suggested and investigated as once-a-day tablet formulations. 1) In that formulation, dissolution medium quickly permeates to the inner layer of water-soluble excipients, and the two barrier layers swell to surround the inner layer rapidly, controlling drug release from the inner layer. After oral administration, the tablet might become fully hydrated quickly and reach the colon where little water is available. The hydrated state of the tablet might induce continuous drug release even in the colon.As an extended study on the technology and to investigate the feasibility as a once-a-day tablet formulation, a hydrophilic model drug (tamsulosin HCl) was selected and various three-layered tablet formulations were evaluated together with their properties. These formulations were also compared with a commercial product, tamsulosin OCAS ® , to achieve more consistent plasma drug concentrations. Additionally, a pharmacokinetic study of the three-layered tablets using beagle dogs was performed in comparison with the results of the reference tablet.Tamsulosin Fig. 1), is a third-generation a1-adrenoceptor (AR) antagonist and has been developed for the treatment of lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH). 2) Among the currently available a1-AR antagonists, tamsulosin is the most frequently prescribed pharmacological therapy due to its favorable selectivity for human prostatic tissue, which is probably related to the a1 A and a1 D -AR subtypes. 3,4) Tamsulosin HCl modified-release (MR) capsules are developed by Astellas Pharma Inc., and marketed under the trade names Harnal, Flomax, Flomaxtra, and Urimax. On the other hand, generic non-modified release capsules are still approved and marketed in many countries such as Canada and the U.S. The tamsulosin MR capsule formulations, however, have some limitations such as food dependent absorption.3) The labeling information recommends that the capsule needs to be taken after breakfast or after the first meal of the day. Lack of compliance with this dosing recommendation may cause increased exposure to the drug, leading to a higher risk of vasodilatation-related adverse effects like dizziness, headache, orthostatic hypotension, and syncope. 5) To reduce the occurrence of the adverse effects, new oral controlled absorption systems have been developed and used to overcome the low absorption properties even from the colon. 6) The OCAS ® formulation is a controlled release system of a gel matrix type, with gel-forming and gel-enhancing components. Polyethylene glycol (PEG), a gel-enhancing agent, is a hydrophilic agent that facilitates water uptake into the tablets. It may ensure very rapid and nearly complete gelation/hydration of a hydrophilic gel-forming agent (i.e., polyethylene oxide (PEO)) in the upper part of the gastrointestinal (GI) tract, stomach, and small int...
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