Razi Journal of Medical Sciences

fa شیبه سازی تغییرات غلظت دارو در هیدروژل‌های متورم شونده با ترکیبات مختلف کیتوسان و ژلاتین بر پایه PVA Simulation of Drug Concentration Changes in Swollen Hydrogels with Different Compounds of Chitosan and Gelatin Based on PVA داروسازی Pharmacy پژوهشي Research زمینه و هدف: یکی از روشهای بهبود سرعت پخش و نفوذ دارو در سامانههای پایه هیدروژلی (متورم شونده)، استفاده از مدل‌سازی ریاضی رهایش دارو است. استفاده از این روش میتواند باعث ایجاد درک بهتری از مکانیسمهای کنترل دارو و رهایش آن شود. هیدروژلها یک ماده زیستی متورم شونده هستند، که برای به کار بردن در رهایش دارو نیاز به کنترل دارند. از این رو هدف از این تحقیق مدلسازی رهایش دارو در هیدروژلهای متورم شونده با ترکیبات پلیمرهای پلی وینیل الکل (PVA)، کیتوزان و ژلاتین است، که در نهایت میتوان به کمک این شبیه سازی زمان و غلظت رهایش دارو را پیش بینی کرد. روش کار: در این مدلسازی تغییرات غلظت دارو در پنج هیدروژل مورد قرار گرفت. برای این شبیه سازی ابتدا از معادلات حاکم بر سیستم رهایش دارو، نرم افزار مهندسی MATLAB و روش حل عددی برای تعیین مکانیسم رهایش دارو در هیدروژل استفاده شد، سپس برای ارزیابی عملکرد هیدروژلها در رهایش دارو نمودارهای دو بعدی و سه بعدی تغییر غلظت دارو در هر هیدروژل مورد بررسی قرار گرفت. یافته ها: مشاهدات نشان داد که با افزایش غلظت کیتوزان نسبت به ژلاتین در ترکیب هیدروژل نرخ تورم هیدروژل افزایش می‌یابد و همچنین رهایش دارو در هیدروژلهایی که تورم بیشتری داشتند نرخ بیشتری را نشان دادند، غلظت دارو در هیدروژل (3:1) Cs:Gel که بیشترین نرخ تورم را داشت، به کمترین زمان (90 دقیقه) برای تخلیه دارو نیاز بود. اما هیدروژل (1:3) Cs:Gel با کمترین نرخ تورم، بیشترین زمان (150دقیقه) برای تخلیه دارو داشت. نتیجه‌گیری: از نتایج شبیه سازی میتوان نتیجه گرفت که در هیدروژلهای با نرخ تورم زیاد غلظت دارو به سرعت کاهش یافت و در هیدروژلهایی که نرخ تورم کمتری دارند، مدت زمان رهایش دارو افزایش پیدا کرد، که دلیل آن اهمیت انتقال جرم از طریق حرکت توده و نرخ تورم است. Background and aims: Changes in drug concentration (release) in the body is one of the most important parameters affecting the health of patients, whose sharp increase or decrease can cause complications in patients. Therefore, it is very important to study the release of the drug and determine the concentration of the drug in the body. Drug release in the human body can be done through various mechanisms that by examining drug release at different times, effectiveness of each mechanism can be determined. Drug delivery systems can be divided into general categories: diffusion-controlled, swelling-controlled, and environmentally sensitive systems, each of which can release the stored drug under different conditions and through different mechanisms. Recently, drug release in swollen hydrogels has attracted many attentions from researchers, indicating the importance of this drug delivery system. Hydrogels are crosslinked polymeric networks that can absorb water more than twenty times their own weight. Depending on their environment, hydrogels can swell or release absorbed water. There are different types of hydrogels that can swell in response to changes in temperature, pH, glucose levels, etc. in the external environment. For example, environmentally sensitive hydrogels can be engineered to initiate drug release at a specific location.  Most of the studies on drug release from swollen hydrogels have been performed experimentally and its modeling has been limited and with many assumptions. Therefore, the aim of this study was to model the drug release kinetics in chitosan (CS), gelatin (Gel) and polyvinyl alcohol (PVA) hydrogels. Methods: Drug release modeling in five hydrogels with different ratios of CS and Gel based on PVA with different swelling rates were compared. First, using Excel software, the swelling rate of each hydrogel was compared to time, then it was used to simulate drug release in each of the hydrogels. In this modeling, using MATLAB software and mass transfer relations, diffusion and bulk motion (hydrogel boundary swelling) mechanisms were numerically simulated and compared. The assumptions applied to solve the equations of changes in drug concentration were such that the concentration of drug around the hydrogel (drug discharge site) was equal to zero and the diffusivity coefficient was considered constant. The output of the modeling was in the form of two- and three-dimensional graphs showing the changes in drug concentration and swelling rate over time. One of the advantages of drug release modeling in swollen hydrogels is the independence of these results from the type of drug. Results: Modeling findings for all hydrogels showed that the mechanism of drug release through mass movement is very important, so that with increasing swelling rate in a hydrogel, less time is required to complete discharge of drug and then drug with higher dose is released in the body. Cs: Gel (1: 3) hydrogel, which is less swollen than other hydrogels, takes longer (150 minutes) to completely discharge the drug. In other hydrogels, the discharge time of the drug decreased with growth in the same way, which showed the effect of growth rate of the drug-carrying hydrogel on required time for drug release which decreased with increasing the ratio of chitosan to gelatin to make the hydrogel. For example, in the Cs: Gel (3: 1) hydrogel, which had the highest growth rate, the drug discharge time was approximately 90 minutes. Hydrogels with less chitosan in their structure had lower swelling rates leading to reduce the rate at which the drug was discharged through the mass movement in the polymer network of the hydrogel, and had a lower mass flux to discharge the drug. The findings of the modeling are consistent with the results of previous studies, so that in the research conducted by Islam et al., CP4 and HG2 hydrogels had highest swelling rate and release of progesterone, dexamethasone and aspirin at pH=6.8. However, at pH = 1.2, CP4 and HG2 had the lowest swelling and drug release rate. Considering the diffusivity coefficient in the equations, the expression of local volume changes in Equation (2) plays an important role in determining the time of complete discharge of the drug from the hydrogel. For drugs that need to be released at low flow rates and fluctuations in drug concentrations may cause side effects, hydrogels with lower growth rates can be used. Hydrogels with higher swelling rates can also be used for drugs that require high concentrations in the body. Conclusion: From the modeling results obtained in this study and the results of previous researches, it can be seen that the mechanism of mass movement in swollen hydrogels is very important, so that in some hydrogels the contribution of drug discharge through the hydrogel boundary swelling is greater than the drug discharge through diffusion. In addition, to determine the contribution of each mechanism, different combinations of hydrogels can be used to produce the drug reservoir, and by reducing or increasing their swelling, the contribution of the mass movement mechanism can be reduced or increased, respectively. In this work, increasing the ratio of chitosan to gelatin increased swelling and consequently the role of mass movement mechanism in drug release. As a result, in order to increase the drug discharge time, the ratio of gelatin to chitosan should be increased, whereby the swelling rate and finally the discharge rate of the drug are reduced.   تورم و آزاد سازی دارو, هیدروژل, مدل‎سازی, ژلاتین, کیتوسان, PVA swelling and Drug release, Hydrogel, Modeling, Gelatin, Chitosan, PVA 42 53 http://rjms.iums.ac.ir/browse.php?a_code=A-10-4937-1&slc_lang=fa&sid=1 d Mohammad Amin Hosseini Moghaddam محمد امین حسینی مقدم s.m.a.h.m1374@gmail.com 3900319475328460054730 3900319475328460054730 Yes Dezful Jundishapur University of Technology, Iran دانشگاه صنعتی جندی شاپور، دزفول، ایران Atefeh Pourjahed عاطفه پورجاهد 3900319475328460054731 3900319475328460054731 No Dezful Jundishapur University of Technology, Iran دانشگاه صنعتی جندی شاپور، دزفول، ایران