Statistical Optimization of Tamsulosin Hydrochloride Controlled Release Pellets Coated with the Blend of HPMCP and HPMC

Abstract

Tamsulosin hydrochloride is a highly selective a 1A -adrenoreceptor antagonist that was developed for the treatment of lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUPS/BPH). Since tamsulosin hydrochloride can have dose-related adverse effects, a controlled release dosage is necessary.1) Moreover, following oral administration of 0.2-0.4 mg tamsulosin hydrochloride, the drug is absorbed from the intestine and is almost completely bioavailable. Therefore, the preferred formulation of tamsulosin hydrochloride provides controlled release that can modulate both the release rate of the drug and the absorption of drug in the intestinal tract. 2)We previously described tamsulosin hydrochloride controlled release pellets prepared using ethylcellulose aqueous dispersion (Surelease ® ) alone or with additives such as sodium alginate, HPMCP.3,4) Addition of HPMCP to Surelease ® effectively provided pH-dependent drug release. Moreover, the addition of HPMC into film coats improves various film-forming properties such as toughness, elasticity and tensile strength. 4,5) In the present study, we applied the coating system containing Surelease ® , HPMC and HPMCP to drug loaded spherical pellets prepared by conventional extrusion/spheronization techniques.Statistical optimization designs have been previously documented for the formulation of many pharmaceutical solid dosage forms. [6][7][8] Additionally, it is a powerful, efficient and systematic tool that shortens the time required for the development of pharmaceutical dosage forms. 9)The objective of the present study was to prepare tamsulosin hydrochloride controlled release pellets coated with a blend of HPMCP and HPMC in aqueous dispersions (Surelease ® ) and statistically determine the optimal levels of these factors using response surface methodology combined with Box-Behnken design. In addition, controlled release pellets coated with the optimized levels of the coating parameters were compared with commercially available controlled release pellets (Harunal ® capsule) using difference (f 1 ) and similarity (f 2 ) factors. Experimental MaterialsThe following materials were gifted: tamsulosin hydrochloride (Reyon Pharmaceutical Co., Korea), poloxamer 407 (Lutrol ® F127, BASF, Germany), microcrystalline cellulose (Avicel™ PH102, FMC, U.S.A.), carbopol 974P NF (Noveon, U.S.A.) and ethylcellulose aqueous dispersion (Surelease ® E-7-19010, Colorcon, U.S.A.). Sodium alginate (Duckalgin ® NSPH) was purchased from Kibun Food Chemica (Japan). Hydroxypropyl methylcellulose (HPMC, Pharmacoat ® 606) and hydroxypropyl methylcellulose phthalate (HPMCP, HP-55) were obtained from Shin-Etsu Chemical (Japan). All other chemicals were HPLC grade.Experimental Design Response surface methodology combined with Box-Behnken design (BBD) 10) was used to ascribe the relationship between the independent variables and the responses as well as to determine the coating parameters for tamsulosin hydrochloride controlled release pellets. A three-factor, three-level BBD with th...

Modified Release 3D-Printed Capsules Containing a Ketoprofen Self-Nanoemulsifying System for Personalized Medical Application

“…However, the thicker 4L PVA shell has shown a unique ability to hold the drug for around 2 h which is considered a suitable duration for assuring the release in the intended location, which is the intestine. For the 2L HPMCP-PEG capsule, the release started only after the transfer to the SIF medium suggesting an enteric coating behavior as HPMCP is only soluble in higher pH . These results also confirm the absence of leakage from the well sealed capsules due to their structure or nonsmooth surface.…”

“…For the 2L HPMCP-PEG capsule, the release started only after the transfer to the SIF medium suggesting an enteric coating behavior as HPMCP is only soluble in higher pH. 35 These results also confirm the absence of leakage from the well sealed capsules due to their structure or nonsmooth surface. Such a delivery system can offer both enteric and sustained delivery of ketoprofen.…”

Development of novel mucoadhesive pellets of metformin hydrochloride

“…HPMC is widely used to increase the rate of sustained-release and it also increases the tensile strength of a formulation. Previously, HPMC has been applied to film coating for the improvement of toughness, elasticity, and tensile strength (Kim et al, 2007). Moreover, the tensile strength depends on the percentage content of HPMC (Sebti et al, 2007).…”