Study On The Sustained Release Proformance Of Hydrochlorothiazide/MCM-41 Drug Delivery System

The long-term goal of Chinese medicine sector pursuit is realizing the role of drug selectively in the lesion, precision controlled-release or release on demand, to extend the drug time, under the premise of satisfying curative effect reducing investment dose in order to reduce the toxicity. Drug carriers is just to achieve this goal, which is a new form of drug delivery combined with pharmacy, materials science, and clinical development. The key of drug carrier technology lies in the choice of carrier material. To obtain the ideal release behavior, the carrier material should have the appropriate physical and chemical properties, the response to environment, biocompatibility, and so on.Mesoporous material have the basic conditions for drug delivery due to its uniform tunable pore size(2-30 nm), the stable framework structure, easy modification, larger surface area, non biological activity, non-toxic, and so on. Simultaneously, the mesoporous molecular sieve can be modified by using the reaction between the surface Si-OH of mesoporous molecular sieves and organic silane reagent in order to improve the release performance of MCM-41.MCM-41 have an regularmesoporous channels,larger surface area (>1000 m2/g), tunable pore size ranged from 2-10 nm, Silica shows high tolerancein vivo, and in fact it is currently being used in some pharmaceutical formulations and MCM-41 type silica has been proposed as a convenient material for both drug and gene delivery. As a strong diuretics drug, hydrochlorothiazide has lower solubility in the water and fast absorption rate in vivo. It can be combined with cardiovascular drug for the treatment of essential hypertension and congestive heart failure. Adverse reactions can be caused after long-term administration because of the smaller dosage of the hydrochlorothiazide (one day needs two or three administrations). It is important to research sustained release preparation of hydrochlorothiazide which can reduce the administration times and adverse reactions.In this paper, the mesoporous molecular sieve MCM-41 is synthesized by microwave radiation method using Cetyltrimethylammonium Bromide as surfactant and sodium silicate as silica source, diuretic dmgs is assembled into the passway of mesoporous molecular sieve MCM-41 by the impregnation,the MCM-41 and drug assemblies are charactered by X-ray diffraction (XRD) , low temperature N2 adsorption-desorption,Fourier Transform Infra-Red (IR). Drug loading rate, drug loading time and the release rate simulated body fluid is determined by ultraviolet spectrophotometer method. The result show that the synthesis of mesoporous molecular sieve possess the rule pore structure and the surface is 1211m2/g, molecular sieve MCM-41 as drug carrier possess shorter drug loading time(t=26h), larger drug loading rate(48%), lower release rate constant. On this basis, MCM-41 with different pore sizes were synthesized by adding definite amount of 1, 3 , 5–trimethyl benzene (TMB), and the diuretic hydrochlorothiazide was introduced into the pores of MCM-41 materials. The MCM-41 materials were characterized by low-temperature N2 absorption-desorption, XRD, FT-IR, TG, et al. Delivery rate of hydrochlorothiazide from MCM-41 materials was examined by ultraviolet spectrophotometer in simulated body fluid. Results showed that the synthesized MCM-41 had a uniform mesoporous structure, the average pore size ranged from 4.0 nm to 5.6nm and drug loading ranged from 33.08-39.13%. Hydrochlorothiazide release from the MCM-41-B is fast. In MCM-41-B with the biggest pore size, it needs 10h to release 79%, whereas the others need 20h. Hydrochlorothiazide release rates reduce with the decrease of pore size and hydrochlorothiazide release rate can be adjusted by controlling the pore size. Following the above experiment results, the aminopropyl was introduced into the MCM-41 which have the biggest pore size by chemical modification. The X-ray diffraction results showed that aminopropyl MCM-41 still obtain the mesoporous structure, there is still a larger drug loading (38.23%) in spite of slightly reducing with pore size, the sustained release system of MCM-41 and MCM-41-(CH2) 3NH2 drug release system is prepared, and these results also provide some experimental data for the further study of the release preparation of MCM-41.