In Vitro Evaluation of Smart Pellets as Intelligent Drug Delivery Systems

In Vitro Evaluation of Smart Pellets as Intelligent Drug Delivery Systems

Mohammad F. Bayan, Balakumar Chandrasekaran, Rahaf M. Allan and Weaam A. Khalaf

Faculty of Pharmacy, Philadelphia University, P.O. Box 1, Amman 19392, Jordan

Email: mbayan@philadelphia.edu.jo

Introduction

The small intestine is where most conventional oral formulations are mostly absorbed. This restricts their usage in the treatment of several colon disorders since the medicine must act topically at the site of inflammation. This opened the door for the development of an intelligent colonic drug delivery system, which enhanced therapeutic effectiveness, decreased dosing frequency and potential side effects, and increased patient acceptance—particularly in situations where enemas or other topical preparations might not be sufficient to treat inflammation alone. This study's primary goal was to develop a smart medication delivery system based on pH-sensitive polymeric formulations made using a free-radical bulk polymerization technique. In the formulations, 5-amino salicylic acid was used as a model drug and Capmul MCM C8 was added to increase bioavailability. The in vitro swelling and release evaluation showed that the developed system may be able to delay drug release under conditions that mimic the stomach and small intestine while triggering it under conditions that mimic the colon, indicating its potential usefulness as a smart colonic drug delivery system.

Materials and Methods

Hydroxyethyl methacrylate (HEMA), Methacrylic acid (MAA), Dimethylaminoethyl methacrylate (DMAEMA), 5-amino salicylic acid, ethylene glycol dimethacrylate (EGDMA), disodium hydrogen phosphate dodecahydrate, azobisisobutyronitrile (AIBN), potassium chloride, sodium chloride, potassium dihydrogen phosphate, BRAND® stopcock grease, sodium dodecyl sulphate, and sodium hydroxide were purchased from Sigma-Aldrich. Capmul® MCM C8 was purchased from ABITEC. Hydrochloric acid (37%) was purchased from Biosolve Chimie.

Preparation of Intelligent Pellets: Nine pellet formulations based on HEMA, MAA, and/or DMAEMA monomers were prepared utilizing a free-radical thermal bulk polymerization technique [1]. The pellets were loaded with 5-amino salicylic acid and capmul MCM C8 as a dissolution enhancer and model drug, respectively. Pellets' Swelling Studies: The pellets' in vitro swelling behavior was examined in a biobase thermostatic shaking water bath SWB-A at 37 °C in buffers with equal ionic strengths at pH 1.2 and pH 7.4. The equilibrium swelling ratio and swelling behavior were examined as previously described by Bayan et al [2]. Pellets' Release Studies: The in vitro release of the model drug (5-amino salicylic acid) was examined using a modified Heelan and Corrigan method in a biobase thermostatic shaking water bath SWB-A working at 100 rounds per minute and 37 °C in buffers of equivalent ionic strength, at pH 1.2 and pH 7.4 [3]. After fitting the first 60% of the release data to the Korsmeyer-Peppas model, the release rate and mechanism of the medication were studied. The two-way analysis of variance test and Tukey's multiple comparison test (n = 3, p 0.05) were used to statistically examine all of the data. The graphics and statistical analyses were created using the GraphPad Prism software, version 9.4.0.

Results and Discussions

Figures 1-2 show the in vitro swelling profile and equilibrium swelling ratio of the pellets at each pH. When comparing the swelling profiles of HEMA-co-MAA pellets at pH 7.4 and pH 1.2, a significantly higher swelling was observed at pH 7.4. This may be attributed to the fact that these polymers' anionic pendant groups (MAA) were more ionized in the simulated intestinal fluid than in the simulated gastric fluid, resulting in stronger electrostatic interactions and increased swelling. At pH 1.2 compared to pH 7.4, the swelling profile for the HEMA-co-DMAEMA pellets was much higher. This may be related to the fact that these polymers' cationic pendant group (DMAEMA) were more ionized in the simulated gastric fluid than in the simulated intestinal fluid. Figures 3-4 display the in vitro release profiles of the produced pellets at each pH. In comparison to the HEMA-co-DMAEMA based pellets (F7-F9), the HEMA and HEMA-co-MAA based pellets (F1-F6) showed a greater ability to delay the release of the model drug at pH 1.2. When compared to the other formulations, the HEMA-co-MAA-based Pellets (F3-F6) showed a greater release rate at pH 7.4. With a cumulative release of almost 75% after 12 hours, F4 had the largest cumulative drug release at pH 7.4. After five hours at pH 1.2, this formulation attained a cumulative release of about 25%. An n value more than 0.5 and less than 1 was obtained for all pellets at pH 7.4 and for F7-F9 at pH 1.2, indicating an anomalous mechanism of drug release. This implies that diffusion and polymer swelling control the drug release in these formulations. At pH 1.2, F1–F6 pellets exhibited a n value lower than 0.5, indicating a Fickian diffusion mechanism.

Conclusions

The in vitro swelling and release investigations showed that F4 may be able to postpone the drug release while it is present in the stomach and small intestine, while triggering its release in the colon. This makes it promising to achieve a colonic-specific delivery for the potential treatment of colon-associated diseases, such as inflammatory bowel diseases. Further work is required to evaluate the in vivo behavior, biocompatibility, and safety of this system.

References

1. Bayan MF, Salem MS, Bayan RF. Development and In Vitro Evaluation of a Large-Intestinal Drug Delivery System. Research Journal of Pharmacy and Technology. 2022, 15(1):35-9.
2. Bayan MF, Marji SM, Salem MS, Begum MY, Chidambaram K, Chandrasekaran B. Development of Polymeric-Based Formulation as Potential Smart Colonic Drug Delivery System. Polymers. 2022, 14(17):3697.
3. Obaidat RM, Tashtoush BM, Bayan MF, T Al Bustami R, Alnaief M. Drying using supercritical fluid technology as a potential method for preparation of chitosan aerogel microparticles. Aaps Pharmscitech. 2015, 16(6):1235-44.