Department of Pharmaceutics, Shree Sureshdada Jain Institute of Pharmaceutical Education & Research Jamner Dist Jalgaon 424206 Maharashtra, India
The goal of the current study was to create vildagliptin tablets with sustained release. Due to its brief biological half-life (2–3 hours), this medication is thought to be appropriate for sustained release tablet formulation in order to extend its therapeutic effect. Vildagliptin is a novel dipeptidyl peptidase-4 inhibitor class of oral antihyperglycemic medication. Materials and Method: Wet granulation was used to prepare the SR tablets, with varying ratios of synthetic polymers. Granules were prepared, and their compressibility index, Hausner's ratio, bulk density, and tapped density were assessed. Utilized Statistical Analysis: The vildagliptin and various polymers' individual and combined Fourier-transform infrared spectra demonstrate the medication's compatibility with excipients. Results: It was discovered that the tablets' physicochemical characteristics were within tolerance. The weight variation, thickness, hardness, percentage friability, percentage drug content, and in vitro release of the prepared tablets were assessed. Using a USP dissolution rate test apparatus II (50 rpm, 37 °C ± 0.5 °C) as the dissolution medium, in vitro dissolution studies were conducted for two hours in 0.1 N HCl (1.2 pH) and then for 10 hours in 6.8 phosphate buffer. Conclusion : The maximum drug release of 91.03% was observed in 12 hours of dissolution for the optimized formulation F5. Formulation F5's release kinetic data revealed zero order (R2 = 9902).
Oral Drug Delivery :
Oral drug delivery method is the most widely utilized routes for administration among all alternatives that have been explored for systemic delivery of drug via various pharmaceutical products of different dosage forms.(1,2,3,4,5) With many drugs, the basic goal is to achieve a steady state blood level that is therapeutically effective and non-toxic for an extended period of time. The design of proper dosage form is an important element to accomplish this goal. Sustained release, sustained action, prolonged action, controlled release, extended action, timed release and depot dosage form as term used to identify drug delivery system that are designed to achieve prolonged therapeutic effect by continuously releasing medication over an extended period of time after administration of a single dose. In the case of oral sustained released dosage form, an effect is for several hours depending upon residence time of formulation in the GIT.(5,6) Conventional drug therapy requires periodic doses of therapeutic agents. These agents are formulated to produce maximum stability, activity and bioavailability. For most drugs, conventional methods of drug administration are effective, but some drugs are unstable or toxic and have narrow therapeutic ranges. Some drugs also possess solubility problems. In such cases, a method of continuous administration of therapeutic agent is desirable to maintain fixed plasma levels. To overcome these problems, controlled drug delivery systems were introduced three decades ago. These delivery systems have a number of advantages over traditional systems such as improved efficiency, reduced, toxicity, and improved patient convenience.(7,8)
Sustained release dosage forms : Any drug or dosage form modification that prolongs the therapeutic activity of the drug. The release of the drug is retarded for a delayed and prolonged period of time in the systemic circulation. Sustained release formulation maintains a uniform blood level of drug with better patient compliance as well as increased efficacy of drug.(9,10,11) Sustained release tablets are generally taken once or twice a day during a course of treatment whereas in conventional dosage forms there is need to take 3-4 times dosage in a day to achieve the same therapeutic action.The regular measurement structures are quickly supplanted by this novel's sustained discharge procedures. The terms Sustained Release, Delayed Release or Prolong Release formulations are utilized to recognize drug delivery systems that are intended to accomplish or expand therapeutic impact by ceaselessly discharging medicine over an all-encompassing period of time after administration of a unit dose.(12,13) Any drug or measurement structure adjustment that draws out the therapeutic action of the drug. The arrival of the drug is hindered for a postponed and delayed period of time in the fundamental circulation.
MATERIALS AND METHOD :
Vildagliptin was purchased from Sun Pharma Industries LTD. Silvasa.
MCC,Lactose, HPMCK100M,Magnesium sterate,talc were purchased from Jinendra Scientific .
Preparation of SR Tablet of Vildagliptin :
Fig no 1 Hydraulic Press
Evaluation of SR Tablet :
1. Appearance:
The tablets were visually observed for capping, chipping and lamination.
2. Tablet dimensions/thickness:
The thickness of the tablets was determined by using vernier callipers. Randomly 10 tablets selected were used for determination of thickness that expressed in Mean ± SD and unit is mm.
Fig. No 2: Thickness determination by vernier caliper apparatus
3. Hardness
The hardness of a tablet determines its resistance to shipping, breakage, storage, transportation, and handling before use. The hardness of 20 tablets from each formulation was determined using the Monsanto Hardness Tester. The tablet was held in between the tester's two jaws along its oblong axis. At this point, the reading should be zero kg/cm2. Then constant force was applied by rotating the tablet fractured.
4. Friability:
Friability is the loss of weight of tablet in the container due to removal of fine particles from the surface during transportation or handling. Roche friabilator was employed for finding the friability of the tablets. For tablets with an average weight of 0.65 g or less take a sample of whole tablets corresponding to about 6.5 g and for tablets with an average weight of more than 0.65 g take a sample of 10 whole tablets. Roche friabilator was rotated at 25 rpm for 4 minutes for 100 rounds. A loss of less than 1% in weight in generally considered acceptable. Percent friability was calculated as follows,
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Percent Friability % F = Initial weight - Final weight/ Initial weight x 100 |
5. Weight variation test:
To determine weight variation, 20 tablets of each formulation were individually weighed using an electronic balance, the average weight was calculated, and the individual tablet weight was then compared to the average value.
Table No. 1: Specification for tablets as per USP
6. Drug content:
Ten tablets from each batch were precisely weighed and powdered. The powdered equivalent to 100 mg vildagliptin was weighed and shaken in 100ml of Phosphate Buffer pH 6.8 in a volumetric flask, and 1ml was pipetted out and diluted up to 10 ml. The resulting solution was filtered and measured at 224 nm, and the vildagliptin content was calculated. It was calculated by using formula,
7. Diameter
Tablet diameter is dependent on the dimensions of the punch tip or punch face so it is critically checked or verified before installation of tooling on the compression machine/other. Example- Suppose we want to compress a batch of tablets in a round shape having a diameter of 8.0 mm. so for this purpose, we will use round-shaped punches & dies. To produce 8.0 mm round tablets the diameter of punches used should always be 8.0 mm.
Tooling Verification-
The tablet diameter testing is an unofficial test so most of the person in the pharmaceutical industry do not give much importance to it, but it is most critical check because if our tablet diameter or dimensions are not according to specifications it will create problems not only during tablet blistering but will also lead to deviation and batch reprocessing.
Procedure For Measuring Tablet Diameter-
Like the tablet thickness test, the diameter of tablets is also measured using vernier calipers. If tablets are round simply, we measure the diameter by placing round tablets in the jaws of the vernier caliper one by one and take readings displayed on the digital vernier caliper.
Fig. No. 3: Determination of Diameter of Vildagliptin SRT by Vernier Caliper
8. In-vitro dissolution studies:
The USP dissolution test apparatus (apparatus II paddle type) was used to study the drug release from the tablets. The dissolution medium was 900ml of 0.1 N HCl. The release was performed at 37±0.5°C, with rotation speed 50 rpm. 5ml of sample was withdrawn at predetermined time intervals and replaced with fresh medium. The samples were analyzed after appropriate dilution by UV spectrophotometer 1800 at 228 nm and drug release was determined by following formula,
RESULT AND DISSCUSSION :
Preformulation Studies:
1.Organoleptic properties of Vildagliptin:
Table No.2: Organoleptic properties of vildagliptin
2 Melting point determination:
Table No. 3. Melting point of vildagliptin:
3 Solubility:
Table No.4 : Solubility of Vildagliptin
Estimation of Vildagliptin:
Fig. No.4: Spectrum of vildagliptin
2 Standard calibration curve of vildagliptin in 0.1 N HCl
Table No. 5. Absorbance of Vildagliptin:
Fig. No 5: Calibration curve of vildagliptin:
Standard Calibration Curve of Vildagliptin in 6.8 pH buffer:
Fig no 6 : Standard Calibration Curve of Vildagliptin in 6.8 pH buffer
Determination of solubility of vildagliptin in water:
Table No. 6. Absorbance of vildagliptin in water
Fig. No.7 : Solubility curve of vildagliptin in water
Fourier Transform Infrared Spectroscopy:
Vildagliptin :
Fig No. 8 : FTIR of vildagliptin
Table No 7: FTIR interpretation of vildagliptin
Fig no. 9 : FTIR spectrum of Vildagliptin + PVPK 30 + HPMC K 100M
Table No .8: FTIR Interpretation of Vildagliptin + PVPK 30 + HPMC K 100M
Fig no. 10: FTIR spectrum of HPMCK 100 M + PVPK30
Table No. 9: FTIR Interpretation of HPMCK 100 M + PVP
Differential scanning colorimetry :
The DSC thermogram showed the sharp endothermic peak at 148.22 ?C represented the melting point of vildagliptin.
Fig No.11: DSC Thermogram of pure vildagliptin
Fig No. 12: DSC thermogram of vildagliptin + all blend
Table No.11: Thermal transition & enthalpy values of vildagliptin & vildagliptin with all excipients
Evaluation of Tablet: Pre-compression parameters of preliminary trial batches of vildagliptin tablet :
Table No.12: Pre-compression parameters of preliminary trial batches of Susatined release tablets of vildagliptin
All precompression parameters of preliminary trial batches shown satisfactory results as per their standard limits.
Table no. 13: Evaluation of Post-compression parameters of preliminary trial batches of Susatined release tablets of vildagliptin
Table No.14 : Post compression parameters of preliminary trial batches of Sustained release tablets of vildagliptin
The post compression parameters of preliminary trial batches showed satisfactory results among all batches (B1-B9)
In-vitro drug release of preliminary trial batches of vildagliptin SRT tablet
Table No.15: % In-vitro drug release
Fig No.13 : In-vitro Drug Release Profile of Preliminary Trial Batches of Susatined Release Tablet of Vildagliptin (B1-B9) Batches.
Evaluation of batches of IRT of vildagliptin generated by CCD:
Table No.15. Pre-compression Parameter of Batches Generated by CCD
Table No.16: Post-compression Parameter of Batches Generated by CCD
Table No.17: Post-compression Parameter of Batches Generated by CCD
Table No.18: % In-vitro drug release of batches by DOE software:
Fig No.14: In-Vitro Drug Released Study of Optimized Batches of Vildagliptin SRT Generated by CCD (B1-B9).
Table No.19: Comparison of Percentage Drug Released of Optimized Formulation (B5) of Vildagliptin SRT of Vildagliptin and Marketed Uncoated Tablet
Fig No. 15: Comparison of In-Vitro Drug Released of Optimized Batch B5 and Marketed Formulation (Vylda 50 mg) Uncoated 2 Tablets of Vildagliptin
Optimization and Data Analysis:
Optimization:
Table No.20: Result of optimization batches by Central Composite Design:
Data Analysis:
Table No.21: Result of Analysis of Variance for Batches by CCD of Vildagliptin Sustained Release Tablet
DF indicates degree of freedom; SS sum of square; MS mean sum of square and F is Fischer’s ration.
Fig No.16 : Response Surface Contour Graph Showing the Influence of Hpmc k100m (A1) and PVPK30 (B1) on % Drug Release (Y1)
Fig No.17 : 3D Response Surface Graph Showing the Influence of HPMCK100M A1) and PVPK30 (B1) on % Drug Release (Y1)
Stability Study:
I) Accelerated Stability Study
Table No.22: Accelerated Stability Data for B5 Optimized Batch of Vildagliptin SRT
II) Long term Stability Study
Table No. 23 : Accelerated Stability Data for B5 Optimized Batch of Vildagliptin SRT
III) Long Term Stability Study (Store in Refrigerator)
Table No 24: Long Term (Stored in Refrigerator) Stability Data for B5 Optimized Batch of Vildagliptin SRT:
Fig No.18: Stability studies of SRT of Vildagliptin in Environmental Test Chamber
CONCLUSION:
In present study an attempt has been made to prepare sustained release tablet. Vildagliptin was used as model drug.Suitable analytical method based on UV Visible spectrophotometer was developed for estimation of VildagliptinThe polymer selected for the sustaining the release i.e HPMC K100M, PVPK30 is compatible with Vildgliptin confirmed by FT-IR analysis.Wet granulation technique was established for preparation of sustained release tablet of vildagliptinPreliminary trail batches of sustained release tablets of vildagliptin were successfully prepared using HPMC K100M , PVPK30 From the results of preliminary batches helps to find out optimum concentration of release retarding polymer.The CCD designs were selected & can be successfully applied for formulation of factorial batches using combination of polymer.The pre & post compression parameter were evaluated and was found within acceptable limit.The selected independent variable exhibit the significant effect on dependent variables.The polymer used showed better control over the percentage drug release.Chosen experimental design was found to be very useful tool in the development of Vildagliptin and allow minimum possible number of experimental run and rapid systematic and reliable screening to identify and quantitively define the significant formulation factor influencing the drug release.
REFERENCES
Abhay Sawant, S. D. Barhate, M. M. Bari, Yogesh Sonawane, Amol Chaudhari, Reema Jagnit, Formulation Evaluation & Optimization Of Vildagliptin Sustained Release Tablet, Int. J. of Pharm. Sci., 2024, Vol 2, Issue 8, 3086-3103. https://doi.org/10.5281/zenodo.13313360
10.5281/zenodo.13313360
