Abstract

The present study outlines a systematic approach for designing and development of Metformin Hydrochloride sustained release matrix tablets. Different formulations were formulated by wet granulation technique using Xanthan gum and HPMC K100M as polymers along with other excipients The formulations were evaluated for their physicochemical properties.

Introduction

I. INTRODUCTION

Oral administration is a more common method of drug administration. The majority of medications taken orally are swallowed, however a small number are designed to dissolve in the mouth. The oral route of medication administration is the most common and has been utilized successfully for traditional drug delivery when compared to alternative routes. It is regarded as the most natural, simple, practical, safe method of giving medications. It also offers greater design flexibility for dosage forms, is inexpensive to produce, and is natural.[1] A tablet is an oral dose type used in medicine. The solid unit dosage form of a medication or medications, with or without acceptable excipients, and manufactured either by moulding or by compression, may be referred to as a tablet. It is made up of a combination of excipients and active ingredients. Typically crushed or compacted from a powder to a solid dosage. The excipients include diluents, binders, or granulating agents, glidants and lubricants to ensure efficient tablet ting; disintegrants to promote tablet break up in the digestive tract; sweeteners or flavors to enhance taste; and pigments to make the tablets visuallor aid in visually appealing or aid in visually appealing or aid in visually identifying an unknown tablet.

A. Sustained Release Matrix Tablet

By delivering prolonged, regulated distribution and/or directing the drug to the targeted place, innovative drug delivery systems play a significant role in enhancing the therapeutic effectiveness of pharmaceuticals that have already been incorporated. Any drug delivery system's goal is to quickly and sustainably attain the required drug concentration by delivering a therapeutic dose of the drug to the targeted spot in the body. [1]The type of delivery system, the ailment being treated, the patient, the length of therapy, and the qualities of the drug are only a few of the linked, significant factors that affect how oral sustained release delivery systems are designed. Any drug delivery system that provides delayed drug release over an extended period of time is a sustain release system. [2]Matrix tablets are regarded as the most economically viable prolonged action dosage forms that require the fewest processing variables, work with standard equipment, and hold huge amounts of medication. There is still interest in creating innovative matrix-based formulations that enable sustained drug release utilizing easily available, affordable excipients. The interest in continuous release drug delivery systems has increased significantly during the past 20 years. This is because of a number of things, including the prohibitive cost of developing new drug entities, the ageing of existing international patients, the development of new polymeric materials useful for delaying the release of drugs, and the advancements in therapeutic effectiveness and safety that these delivery systems have made. Nowadays, veterinary products are now using the technology of sustained release. [3]

B. Mechanism of Drug Release

The diffusion or disintegration of the medication is one of the mechanisms involved in its release. Hydration of the matrix occurs when it is exposed to an aqueous solution; as a result, it swells to close off any existing pores and the contents dissolve. Gel formation results in the production of a viscous solution, which creates a positive pressure that prevents liquid entrance and leads to matrix disintegration.

The purpose of the current study was to prepare metformin hydrochloride sustained release matrix tablets using different concentrations of natural and synthetic polymers (Xanthan gum) and to analyze the stability, in-vitro release characteristics, and effects of the prepared formulations

II. MATERIALS AND EQUIPMENTS

A. List of Materials and Supplier

Metformin hydrochloride (Aarti pharmaceuticals,Mumbai ). HPMC K100M (SGRS college of Pharmacy). Xanthan gum (SGRS college of Pharmacy ). Sodium bicarbonate (SGRS college of Pharmacy). PVP k3 (SGRS college of Pharmacy).

Microcrystalline cellulose (SGRS college of Pharmacy). Talc (SGRS college of Pharmacy). Magnesium stearate (SGRS college of Pharmacy).Aerosil (SGRS college of Pharmacy)

B. List of Equipment and Manufacturer

Electronic Weighing Balance (Shimadzu, Mumbai )(Model: AU220) Rotary tablet compression machine( Karnavati Engineers Pvt. Ltd, Mumbai) (Model: MINI PRESS- II MT). UV Spectrophotometer ( Jasco, Japan) (Model: V-530 &V-630). FTIR Spectrophotometer (Shimadzu, Japan) (Model: FTIR- 8400$). Differential Scanning calorimeter ( Mettler Tolendo, Mumbai) (Model: Stare SW 920). USP Tablet Dissolution Apparatus (Electro lab, Mumbai) (Model: TDT-06P). Tap density tester( Labinda, Mumbai) (Model: TD1025). Roche friability tester( Labinda, Mumbai) (Model: FT1020). Hardness tester ( Labinda, Mumbai) (Model: TH 1050 M). pH Meter( Labinda, Mumbai) (Model: GMPH).

C. Diabetes Mellitus

When your blood sugar (glucose) level is too high, you develop diabetes. It happens when your body doesn't process insulin effectively or when your pancreas doesn't produce any insulin at all. All ages are impacted by diabetes. Diabetes comes in a variety of forms, the majority of which are chronic (lifelong) and treatable with medication and/or dietary modifications.

Metformin HCl

Metformin HCl helps to control the amount of glucose (sugar) in your blood. It decreases the amount of glucose you absorb from your food and the amount of glucose made by your liver. More effective than traditional delivery systems are formulations with sustained release. Especially for the treatment of chronic disorders and long-term therapeutic effect Due to this, sustained release dosage forms of metformin hydrochloride are required for the treatment of type-2 diabetes mellitus.

Structure

D. Method Of Preparation

1. Wet granulation
2. Direct compression
3. Dry granulation

III. PREFORMULATION STUDY OF METFORMIN HYDROCHLORIDE

1. Organoleptic Properties: The obtained sample was examined for its appearance, color and odor and observations are reported.
2. Solubility: The solubility of compound was determined methanol, water, pH 6.8 Phosphate buffer,HCl
3. Melting Point: Melting point of the metformin hydrochloride was determined by open capillary tube method using Thiele’s tube. One sided closed capillary filled with drug attached to graduated thermometer and put into the Thiele’s tube contains paraffin oil and constant heat was supplied to the assembly. Temperature was noted at which solid drug changed into liquid. The melting point is 224-228 reported.
4. UV-Visible Spectroscopy: The Metformin hydrochloride was dissolved in methanol, was scanned between 200-400 nm to determine its absorption maxima. The UV spectrum of metformin hydrochloride.
5. Fourier Transform Infrared (FTIR) spectral Analysis: The compatibility of drugs and excipients used under experimental condition were studied. The study was performed by preparing KBr pellets with the help of KBr press taking 1 mg sample in 100 mg KBr. The scanning range was 400 to 4000 cm-1 and there solution was 1cm-1.
6. Differential Scanning Calorimetry: The DSC thermo gram of metformin hydrochloride was carried out to confirm its purity. The DSC thermo gram was recorded on Differential Scanning Calorimetry. Metformin hydrochloride was heated in crimped aluminum pan with a pierced lidat a scanning rate of 100C/min in an atmosphere of nitrogen flow (40mL/min) in the range of 40 to 200oC. DSC thermo gram ofMetformin hydrochloride are depicted.
7. Drug-Excipient Compatibility Study: The drug and excipient compatibility study of selected tablet of formulations performed by FTIR and DSC

A. Formulation of Sustained Release Matrix Tablet OF Metformin HCl

1)  Design of Factorial Batches

A 32 factorial design was implemented for optimization of sustained release matrix tablet formulation of Metformin HCl. According to the model it contained 2 independent variables at 3 levels- +1, 0 and -1. According to model, total nine formulations are possible, the composition of different formulation are shown in Table he different independent variables were- concentration of Xanthan gum (X1) and concentration of HPMC K100M (X2).

Conclusion

1) Metformin hydrochloride is mostly used in the treatment of Type 2 Diabetes, it lowers the blood sugar by causing the pancreas to produce insulin. 2) In this study the attempt was made to develop once a day sustain release tablet of metformin hydrochloride by using different polymers Xanthan gum and HPMC K100 as a polymer, magnesium sterate as lubricant, talc as anti-adherent, MCC as filler and PVPK30 as a binder, Aerosil as glidant. In this study attempt was made to findout the effect of natural and synthetic polymer on drug release. 3) To confirm compatibility of natural and synthetic Polymer. To study the effect of various excipient in formulation of sustain release tablet. Metformin hydrochloride is first considered for their purity by performing several tests. 4) It was found that the tablets showed more than 98% drug released in 12 hrs .The release data indicated zeroorder release pattern. The release rate and the pattern indicated the suitability of the dosage form. 5) The results of accelerated stability studies carried out according to ICH guidelines indicated that the tablets did not show any physical changes (color change. friability and hardness), assay and dissolution characteristics during the study period. 6) The study was undertaken with the aim to formulate and evaluate matrix tablets of Metformin hydrochloride using various concentrations of polymers. From the above results and discussion, it is concluded that F-9 formulation of tablet of Metformin hydrochloride containing Xanthan gum and HPMC k100 showed desired drug release. Therefore batch F-9 was considered as optimized formula for preparation of Metformin HCl sustained release matrix tablet using wet granulation method.

References

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Copyright

Copyright © 2023 Padmaja K. Mhaske, Nilesh R. Bhosale, Rajashri S. Chavan, Pavan P. Kondewad, Kunal D. Jadhav. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.