Venkadesh, M (2017) Design and Develop Bilayered Oral Sustained Matrix Tablets of Pioglitazone Hydrochloride and Metformin Hydrochloride. Masters thesis, J.K.K. Nattraja College of Pharmacy, Kumarapalayam.
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Abstract
AIM AND OBJECTIVES: The aim of this investigation is to Design and Develop Bilayered oral sustained matrix tablets of Pioglitazone hydrochloride and Metformin hydrochloride. The concept of Bilayered tablet technology is utilized for stabilization of two incompatible drugs, taste masking of drugs, delivering two drugs having synergistic effects or to deliver a drug for biphasic drug release profile and for the purpose of extension of patents. A Bilayered tablet comprises of two layers among which the first layer is immediate release layer for sudden onset of action and the second layer is Sustained release layer to maintain the steady state concentrations of drug in the blood. Pioglitazone HCl is thiazolidinedione (TZD) class of drug with hypoglycemic, antihyperglycemic and antidiabetic action. Chemically Pioglitazone is (RS)-5-(4-[2-(5- ethylpyridin-2-yl) ethoxy] benzyl) thiazolidine-2, 4-dione. Pioglitazone is used for the treatment of diabetes mellitus type 2 (previously known as non-insulin-dependent diabetes mellitus, NIDDM) in monotherapy and in combination with a sulfonylurea, Metformin. Pioglitazone has also been used to treat non-alcoholic fatty liver. Pioglitazone has also been found to reduce the risk of conversion from prediabetes to diabetes mellitus type 2 by 72%. It has short biological half life of 3-5 hrs (Ramesh et al). Metformin HCl is a biguanide oral anti hyperglycemic (anti diabetic) agent. It is used as an adjunct to diet and exercise for the management of type 2(non-insulindependent diabetes mellitus) diabetes mellitus in patients whose hyperglycemia cannot be controlled by diet alone. As Metformin HCl possess short biological half life (1.5-4.5 hrs), patient should go for frequent administration usually twice or thrice a day which might be a risk to the patient. In order to overcome this Metformin HCl sustained release dosage forms are formulated (Ramesh et al). SUMMARY AND CONCLUSION: In the present investigation, Sustained release Bilayered tablets of Pioglitazone HCl and Metformin HCl were formulated by Direct Compression technique and Wet Granulation technique. Bilayered tablets comprise of IR for sudden onset of action formulated with Crospovidone and SR layer formulated with Polyethylene oxide (PEO- 303) and Carbopol 971 P inorder to sustain the drug release. Drug-excepient compatibility were studied by FT-IR spectral analysis, the results revealed that there were no interactions between drug and excepients in this investigation for the development of the Bilayered tablet formulation. The Precompressional parameters for IR, SR layer formulations ie; Angle of repose, Bulk density, Tapped density, Compressibility index, Hausner’s ratio were studied and found to be in satisfactory limits indicating that the Physical mixtures of the formulations are suitable to formulate the Bilayered tablets. Postcompressional parameters for Bilayered tablets ie; Weight variation, Hardness, Friability, Drug content, were evaluated and the results obtained were satisfactory. The in-vitro drug dissolution studies were carried out for the formulations in pH 1.2 and pH 6.8 phosphate buffer for 2hrs and 10hrs respectively and based on the in-vitro drug release profile IR layer formulation (F3) was optimized for the further development of Bilayered tablets. The formulation F8 comprising of PEO-303 and the formulation F13 comprising of CARBOPOL 971P sustained the drug release for a period of 12 hrs. Dissolution profile of formulations F8 and F13 were compared with the dissolution profile of marketed formulation and Similarity factor for the formulations F8 and F13 was found to be 51.41 and 51.21 respectively.The similarity factor (f2) was also calculated in order to compare optimized formulation (F8 and F13) with that of the reference formulations. Comparission of the profiles indicated that the formulations (F8and F13) had a profile similar to the reference formulation (f2 = 51.41and 51.21) respectively. So these two formulations were comparable with the marketed formulation. The conclusions drawn from the results include: Pioglitazone HCl and Metformin HCL and the excepients selected for this investigation were compatible and it was confirmed by FT-IR studies. Precompressional and Postcompressional parameters were found to be within the satisfactory limits and hence suitable to formulate Bilayered tablets. The order of cumulative % drug release from IR layer formulations was found to be F3>F2>F1. The IR layer formulation ie; F3 was optimized because it released the maximum amount of the drug. The results of in-vitro drug release profile of Bilayered tablets depicts that increase in polymer concentration, increases the retardation of drug release from the SR layer of a Bilayered tablet. The desired drug release rate obtained for F8 and F13 was found to be near to that of the theoretical desired drug release rate. The desired drug release rate obtained for F8 and F13 was found to be near to that of the drug release rate of Marketed formulation. The formulations F8 and F13 were suitable to sustain the drug release for a period of 12hrs, followed first order kinetics exhibited Higuchi’s model and Krosmeyer Peppas exponential coefficient ‘n’ < 0.5 indicates that the release was governed by Fickian diffusion. Hence can conclude that formulated Bilayered tablets of Pioglitazone HCl and Metformin HCl were developed successfully with IR layer comprising of Crospovidone and SR layer comprising of PEO-303 and CARBOPOL 971P as polymers by Direct Compression technique and Wet Granulation technique. From the above results it can be concluded that by using PEO-303 and CARBOPOL 971P we can successfully formulate Bilayer tablets of Pioglitazone HCl and Metformin HCl which showed sustained drug release up to 12hours.
| Item Type: | Thesis (Masters) |
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| Uncontrolled Keywords: | Bilayered Oral Sustained Matrix Tablets ; Pioglitazone ; Hydrochloride ; Metformin Hydrochloride. |
| Subjects: | PHARMACY > Pharmaceutics |
| Depositing User: | Ravindran C |
| Date Deposited: | 19 Dec 2017 07:19 |
| Last Modified: | 19 Dec 2017 09:42 |
| URI: | http://repository-tnmgrmu.ac.in/id/eprint/4473 |
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