Preparation and pharmaceutical evaluation of new sustained-release capsule including starch-sponge matrix (SSM).
The focus of current study was to demonstrate a new sustained-release capsule including starch-sponge matrix (SSM) and to investigate how the pharmaceutical properties of SSM affect the drug release or its pharmacokinetic properties. Three representative drugs (uranine [UN], indomethacin [IMC] and nifedipine [NFP]) with different physicochemical properties (LogP(ow): 0.10, 1.18 and 3.23, respectively) were selected as model drugs. Model drug was dispersioned in pastelike cornstarch (starch glue) after heating 2.0-3.0% cornstarch suspension with electromagnetic wave at 2450 MHz (700 W) for l min. Then the drug mixture was encapsulated into a gratin capsule by a syringe, and the SSM including drug was prepared by means of a freeze-dried method. Essentially, drug-free SSM has a porous and netlike structure, and the distribution aspect of model drugs in the SSM depends on physicochemical properties between cornstarch glue and drugs. UN with much lower lipophilicity exists in continues phase of SSM, and IMC or NFP with a moderate or a higher lipophilicity exist in continues phase or porous space of the SSM. In the in vitro dissolution study, the release rate of drug from the SSM was mainly dependent on the lipophilicities of drugs, showing a rank order of the release rate of UN>IMC>NFP. In addition, the in vitro release rate for each drug was well regulated by changing the initial concentration of cornstarch suspension. In vivo absorption studies after intraduodenal administration of SSM capsule including model drug revealed that the sustained-release effects also could be regulated by the initial concentration of starch suspension. Moreover, the sustained-release effect of SSM capsule was enhanced with an increase in the lipophilicity of drug, and local-residential and mucoadhesive properties of SSM in the intestine provided stable supply of drugs from the SSM. The SSM capsule we developed here shows promising results as an oral drug delivery system for sustained-release regulation or target specificity.
Shibata
Nobuhito
N
Department of Biopharmaceutics, Faculty of Pharmaceutical Science, Doshisha Women's College of Liberal Arts, Kyotanabe, Kyoto 610-0395, Japan. nshibata@dwc.doshisha.ac.ip
Nishumura
Asako
A
Naruhashi
Kazumasa
K
Nakao
Yurie
Y
Miura
Rieko
R
D000268:Adhesiveness; D000818:Animals; D002214:Capsules; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D055590:Electromagnetic Phenomena; D019793:Fluorescein / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D005612:Freeze Drying; D007213:Indomethacin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D007408:Intestinal Absorption; D008297:Male; D009543:Nifedipine / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D016062:Porosity; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013213:Starch / Q000737:chemistry*
D002214:Capsules; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D013213:Starch; D009543:Nifedipine; D019793:Fluorescein; D007213:Indomethacin