Formulation Variation and in Vitro-in Vivo Correlation for a Rapidly Swellable Three-Layered Tablet of Tamsulosin HCl

Abstract

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...

Development of Novel Tamsulosin Pellet-Loaded Oral Disintegrating Tablet Bioequivalent to Commercial Capsule in Beagle Dogs Using Microcrystalline Cellulose and Mannitol

“…The Tmax of a commercial tamsulosin-loaded immediate-release formulation in beagle dogs has been reported to be within 1 h [36]. In this study, both formulations showed an increased T max , indicating a sustained release pattern [37]. Moreover, no significant differences were observed in their pharmacokinetic parameters, including AUC, C max , and T max (45.988 ± 15.345 vs. 46.251 ± 14.245 h•ng/mL; 7.237 ± 2.324 vs. 7.625 ± 2.634 ng/mL; 2.833 ± 0.718 vs. 2.917 ± 0.515 h, respectively).…”

Biopharmaceutical characterization of levothyroxine sodium immediate-release tablets

“…Da bi se uspostavila korelacija nivoa A koja bi bila prihvaćena od strane regulatornih organa u svrhu biowaiver-a, ovaj model korelacije mora biti validiran i razvijen na najmanje 3 formulacije različitih brzina rastvaranja [111]. U literaturi se mogu naći i primeri uspostavljanja IVIVK nivoa A za samo jednu formulaciju [149][150][151]. Iako ovakvi modeli nemaju regulatorni značaj, oni mogu značajno doprineti razvoju relevantnog testa brzine rastvaranja i mogu dodatno biti prošireni u pravu IVIVK nivoa A. Kako profil in vivo brzine rastvaranja nije moguće direktno meriti, za njegovu procenu koriste se različiti matematički modeli izračunavanja.…”