Senthilnathan, B (2012) Design and Development of Pulsatile Drug Delivery System for Anti-diabetic Drug. Doctoral thesis, The Tamilnadu Dr. M.G.R. Medical University, Chennai.
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Abstract
Pulsatile drug delivery system are recently introduced system to deliver the drugs at the specific site of action at the right time and in the required concentration, which are designed according to the circadian rhythm of the body and it is most suitable, convenient, safe, economic and highly efficient method to deliver the drug. Miglitol is a drug commonly used in the management of Type 2 diabetes mellitus which belongs to the category of alpha-glucosidase enzyme inhibitor. Miglitol delay the absorption of carbohydrates from the gastrointestinal tract, thereby limiting postmeal plasma glucose excursions. As the chronological behavior of diabetes mellitus confirms increased blood glucose level after meal (postmeal hyperglycaemia) which is associated with increased risk of retinopathy, carotid intima-media thickness (IMT), oxidative stress, inflammation and endothelial dysfunction, decreased myocardial blood volume and myocardial blood flow, increased risk of cancer, impaired cognitive function in elderly people with Type 2 diabetes. The biological half life of Miglitol is 2 hrs. Hence, by conventional dosage form it needs to be administered three times a day. These conditions demand the development of pulsatile drug delivery system for Miglitol to prevent the complications caused by postmeal hyperglycemia by delivering the drug Miglitol immediately after a meal. The development of pulsatile drug delivery systems for the anti diabetic drug Miglitol encompasses three pulses of drug in a unit dosage forms. Thus the main aim and objective of this work is to enhance the therapeutic efficacy of Miglitol by timed release, minimize complications due to postmeal hyperglycemia, reduce dosing frequency and achieve better patient compliance. To achieve the above goals two pulsatile drug delivery systems are designed: 1. Pulsincaps, 2. Press coated tablets. The prepared dosage forms were optimized and evaluated in vitro and in vivo. The preformulation studies were carried out for the drug and excipients to develop thefinal formulation. Drug excipient compatibility studies suggested that there was no interaction between Miglitol and other excipients used in the formulation of Miglitol pulsincaps and press coated tablets. Miglitol pulsincaps were formulated using, body of the capsules with modified solubility; Miglitol immediate release tablets and hydrogel plug of various hydrophilic polymers in different concentrations. The results of the in vitro release studies showed that the formulation MPC9 was found to ideal for pulsatile release. The maximum in vitro drug release of 99.76% (first pulse), 99.81% (Second pulse), 99.92% (Third Pulse) and the desirable lag time 4 hours was obtained for the Miglitol pulsincaps prepared with 60 mg of HPMCK4 M as hydrogel plug (MPC9). Miglitol press coated tablets (MPT1-MPT24) were prepared with varying proportions of hydrophilic polymers (HPMC and L-HPC) and hydrophobic polymers (Glyceryl behenate and Ethylcellulose) alone and in combinations as barrier layer to achieve desired lag time. The ideal concentrations of hydrophilic and hydrophobic polymers were selected based on the results of the in vitro drug release studies and lag time. The in vitro dissolution study results showed the maximum drug release (99.85% for first pulse, 99.43% for second pulse and 99.76% for third pulse) with a lag time of 4hrs for the Miglitol press coated tablets prepared using glyceryl behenate 25 mg and L-HPC175 mg (MPT24) as barrier layer. The selected formulations of Miglitol pulsincaps and press coated tablets (MPC9 and MPT24) were subjected for pharmacokinetic and pharmacodynamic studies using male albino rabbits. Pharmacokinetic changes in all the formulations analyzed were almost similar as standard marketed drug. All the parameters altered in both the formulations treated groups were found to be within biological limits. No major changes were observed when compared to standard formulations. Hence it can be summarized that the pharmacokinetic changes among the tested groups were comparable with that of standard pure and standard marketed formulations. No remarkable deviations have been identified in both kinetic and dynamic parameters in the animal models used in this present investigation. The results of these studies revealed that the in vivo release of Miglitol pulsincap and press coated formulations correlated with release pattern of standard marketed Miglitol tablets. The extended Tmax, and Cmax confirms the delayed release of formulation. The optimized formulation of Miglitol pulsincap (MPC9) and press coated tablets (MPT24) were subjected to stability studies as per ICH guidelines. No significant changes in the physical and chemical characteristics were observed during the stability studies of Miglitol pulsincap (MPC9) and Miglitol press coated tablets (MPT24). The optimized Miglitol pulsincaps(MPC9) and Miglitol press coated tablets were evaluated for its in vitro drug release profile and compared with the in vitro drug release profile of marketed conventional Miglitol tablets. Studies of in vitro drug release of Miglitol pulsincaps (MPC9) exhibited the maximum drug release 99.77±0.09% for first pulse, 99.82±0.19% for Second pulse and 99.91±0.11% for third Pulse. The lag time after each drug release was found to be 4hrs.The in vitro dissolution study of Miglitol press coated tablets (MPT24) exhibited the maximum drug release 99.84± 0.07% for first pulse, 99.42± 0.34 % for second pulse and 99.74± 0.16 % for third pulse with the lag time of 4hrs after each drug release. The in vitro drug release for the Miglitol marketed conventional tablets were carried out in buffer solution pH1.2. The cumulative percentage drug release at different time intervals such as 15, 30, 45, 60, 90 and 120 mts were 38.55±0.18, 68.97±0.25, 89.76±0.19, 97.85±0.55, 99.17±0.27 and 99.20±0,46 respectively. CONCLUSION The present study was made to develop the pulsatile drug delivery of Miglitol. Pulsincap and press coated tablets for the timed release of Miglitol were formulated and evaluated. Miglitol pulsincap prepared with different concentrations of hydrogel plug of gelatin, HPMC K4M and sodium alginate were optimized by conducting various trials. Press coated tablets of Miglitol were prepared with different ratios of glyceryl behenate, ethyl cellulose, HPMC and L-HPC that were optimized. The optimization procedure aided in the preparation of pulsincap and press coated tablets of Miglitol with lag time up to 4 hrs. The in vitro dissolution studies revealed that the formulated pulsincap and press coated tablets of Miglitol released the desired concentration of the drug at pre-determined time points. The animal studies confirmed that the pharmacokinetic and Pharmacodynamic parameters of Miglitol press coated tablets and pulsincap formulations were comparable to standard Miglitol marketed tablets. The stability studies on the selected formulation of Miglitol pulsincap and press coated tablets were found to be stable. Comparative studies on in vitro drug release profile of Miglitol pulsincap and press coated tablets were found to have three pulses of drug release with desirable lag time when compared to the marketed conventional Miglitol tablets which contains only single dose of drug. Hence it may be concluded that the newly formulated pulsatile drug delivery systems of Miglitol produce effective control of the increased blood glucose level after intake of meals by allowing the drug to release after a lag time (after meals).
| Item Type: | Thesis (Doctoral) |
|---|---|
| Uncontrolled Keywords: | Design, Development, Anti-diabetic Drug, Pulsatile Drug Delivery System. |
| Subjects: | PHARMACY > Pharmacy Practice |
| Depositing User: | Devi S |
| Date Deposited: | 27 Jun 2017 10:37 |
| Last Modified: | 11 Sep 2022 12:37 |
| URI: | http://repository-tnmgrmu.ac.in/id/eprint/455 |
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