| [Objective] to pediatric antifebrile acetaminoPHen (APAP) preparation to win min gel preparation for external use only, by percutaneous absorption, avoid gastrointestinal first effect, increase medication compliance of the child, to develop a new dosage form for pediatric antifebrile.[Methods]1. The applicability of APAP gel preparation research part, in design before prescribing drugs, the basic PHysical properties, chemical properties and preparations of nature, through the research of oil-water partition coefficient of APAP determination of its solubility in water, the stability of the PH of APAP in experiment environment, with reference to relevant PHarmacopoeia standards, for of APAP by ultraviolet spectroPHotometric method determination, to guide the research of the next step of formulation and process.2. The screening part of APAP gel matrix, from natural high polymer as the main raw material, on the basis of the literature and the preliminary experiment, optimizing suitable for external use win min of hydrogel matrix combination, preparation as drug carrier, choice of chitosan (CS)/poly (vinyl alcohol)(PVA)/glycerol sodium PHosPHate (beta-GP), mooring los sharm407mooring los gresham (F127)/188(F68)/poly (vinyl alcohol)(PVA) gel matrix in both groups, with gel temperature, viscosity, gel strength, and to take off the water as an index, gel prescription was optimized by using orthogonal design, and the gel viscosity thermal stability investigation;3. The research part of APAP gel preparation, quality standard, in accordance with the requirements of the2010edition of China PHarmacopoeia standard to carried on the detailed investigation, the quality of APAP gel build APAP gels detection method, and verifies the methodology, the quality standard of APAP gel are studied.4. APAP gels biological adhesion and in vitro release study part, investigates the biological adhesion of the gel, drug-polymer interactions; By Franze absorption pool with fresh rabbit skin in vitro permeation experiments, examining the cumulative release a quantity to gel.Part5. APAP win min gels skin irritation test, refer to\"acute skin irritation/corrosion test method for chemical skin irritation experiments (GBT21604-2008)\", to observe the skin daub blank gel, dosing gel after local will cause reversible inflammatory changes and irreversible tissue damage. Will adopt self control, gel matrix a (or more) coated in New Zealand white rabbit skin, within the prescribed time interval, observe the degree of local animal skin stimulation and evaluation, to evaluate subjects to cutaneous stimulation.[Result]1. The applicability of APAP gel preparation research part, acetaminoPHen in the water solubility of45.62g/L, that the drug is slightly soluble in water, slightly soluble in PH5.0and PH7.0buffer solution.At37℃,P=5to PH=7high solubility of weak acid environment, both in more than50g/L. Determination of PAPP values under different Ph buffer solution, you can see under the condition of different Ph distribution coefficient between2.6to2.8, with the increase of Ph environment, distribution coefficient decreases gradually, in the Ph=5or so appear upward inflection point, but overall difference is very small, evidence of acetaminoPHen in this experiment is stable in weak acid environment, comply with the requirement of experiment.2. The screening part of APAP gel matrix, through the research on thermal stability of gel, it can be seen that P407and PVA concentration on the sensitivity of the viscosity is not big, but still has a tendency to increase the viscosity increase with increasing temperature, and the influence of PVA concentration on the viscosity of P407; Of various additives on the gel IGT, research on the effects of gel viscosity, by the introduction of P188makes the gelation temperature and salts on the formation of the gel effect is significant, add salt, in addition to CaCl:outside, all can make the solution viscosity increased. In the selection of anion, the impact on the gel viscosity and gelling temperature sequence is:the SO42-> PO43-> Cl-, these ions significantly increased the viscosity of the solution, and reduce the gelation temperature, and cation Ca2+is made to reduce the viscosity of the solution, and at the same time make the gel temperature. Two matrix composite factors three levels orthogonal experiments respectively, due to the optimal combination of PVA/CS/GP does not meet the requirements, gelation temperature and viscosity, PVA/P407/P188combination all the indexes meet the requirements, to optimize the prescription of4.5%PVA,5.5%23%P407and P188,34℃,30seconds can happen in gelation, PVA/P407P188gel preparation technology is simple and feasible, win min resistance, is suitable for the matrix as late dosing experiments.3. The research part of APAP gel preparation, quality standard, the sure win min gel matrix, the optimal combination on the basis of perfecting the preparation prescription, and will be made of finished products in accordance with the2010edition PHarmacopeia gels, part two\"acetaminoPHen gels\" standard methods, such as, of APAP win min gels for quality inspection, and formulate the acetaminoPHen win min gel quality standards, through the investigation, trial production by three batch preparation conforms to the requirements.4. APAP gels biological adhesion and in vitro release study part, with IGT as indicators to investigate matrix drug loadings, the biggest join APAP indeed significantly improve gel IGT, when the dosage is greater than0.1g, gel insolubles, solution gradually become turbid, longer on gelation time, IGT than37℃; When the dosage is0.2g, gel to form gel within30minutes; Drug release in vitro experiments, in order to accumulate percutaneous release a quantity to time curve drawing, visible APAP gel preparation of percutaneous absorption and time has a certain relevance, and release rate is constant, unit area after1.5h ShenTouLiang release is accelerated, after6.0h, release a quantity to turning points, four hours behind only released less than1mg, within10h, drug biofilm by released a total of90.55%dosage, although through the skin directly through to a large number of drugs through several cortex absorption, but the experiment could still prove to berth los sharm for substrate ingredient win min gel has certain the in vitro release of sex, and have obvious sustained release effect.Part5. APAP win min gels skin irritation test showed that acute acetaminoPHen gel or more times after percutaneous drug delivery for skin, or mild skin irritation, thus for percutaneous acetaminoPHen gel provides experiment basis for drug safety.[Conclusion] AcetaminopHen win min gel preparation of main drug acetaminopHen clinical curative effect, fever has hundreds of years of inspection, regular dose very safe; Its synthetic technology mature, stable quality, low price; Preparation for convenient, good children compliance; Can avoid the enterohepatic first effect; Points of measurement accurate, easy to use, storage, with good performance and transdermal drug release effect; Preparation itself without any side effects to the skin, stimulating, it can be made into topical win min preparations to become a future new way for the treatment of colds. |
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