Formulation and Evaluation of Sustained Release Pellets of Oral Antidiabetic Agent by Using Natural Polymer

The therapeutic efficacy of medications is greatly increased by sustained drug delivery systems.  In sustained release drug delivery systems, drug release-retarding polymers are the main players, and numerous natural, semi-synthetic, and synthetic polymeric materials have been studied for this purpose.  In addition, a number of polymers are frequently used in the development of innovative drug delivery systems, such as those that direct drug administration to a particular area of the gastrointestinal tract or that release the drug in reaction to external stimuli.  The two primary components of any pharmaceutical formulation are the active ingredient and excipients.  Excipients aid in the production of dosage forms and enhance their physicochemical characteristics. Research on the application of natural polymers and their semi-synthetic derivatives in medication delivery is still ongoing.  The most effective polymers in matrix systems are those that delay drug release.  Various polymers have been studied as drug retarding agents, each presenting a different approach to the matrix system.  Matrix systems are often divided into three primary categories based on the characteristics of the retarding polymer: plastic, hydrophilic, and hydrophobic.  The best polymers for delaying drug release are hydrophilic ones, and their application in sustained drug administration is gaining traction (9).  Numerous natural polymers have been studied for their potential as sustained release agents. Creating oral sustained release metformin hydrochloride pellets using natural polymers as a rate-controlling component was the main goal of this project.  The current study investigated the possibility of using natural polymers as an excipient source.  The goal is to create a naturally occurring polymer from Blepharis repens that can be used as a retardant and release rate modifier.  The natural polymer's separation, characterization, and application as a natural retardant are covered in this paper.

MATERIAL AND METHOD

The Blepharis repens plant was collected from the Buldhana region during the winter season. The sample was used for evaluation studies, and the natural polymer's physical state, appearance, color, odor, taste, flow properties, angle of repose, bulk density, tapped density, cars index, Hausner's Ratio, solubility, pH, and viscosity were all examined. Additionally, the natural polymer's extractive value was examined.

Formulation of pellets by using natural polymer & API:

A limited quantity of capsules are filled manually.  Granules with 500 mg of metformin hydrochloride as the active ingredient were precisely weighed and then put into capsules using a spatula.

Evaluation of Metformin Hydrochloride capsule

Weight variation:

The average weight was calculated after a random selection of capsules was made.  After that, each capsule was weighed separately, and the weights of each were compared to the average.

Disintegration test: Place one capsule in each tube, then hang the device in a beaker filled with 60 milliliters of water at 370 degrees Celsius.  The disc may be added if hard capsules float on the water's surface.  After 30 minutes of operation, take the assembly out of the liquid and note any residue that is still visible on the device's screen.

Drug content

Each formulation's capsules were taken, and the pellets were extracted.  After transferring the amount of pellets equal to 10 mg of the drug into a 100 ml volumetric flask and dissolving it with distilled water in a sonicator for 10 to 15 minutes, the mixture was filtered, the appropriate dilutions were made, and the absorbance was measured at 234 nm using a UV spectrophotometer.

In-Vitro dissolution release:

Dissolution test apparatus -1; USP-32; 0.1N HCl as the dissolution media; 900 ml; 37 + 0.5 0C as the temperature; and 50 rpm as the speed.

Procedure:

The dissolving vessel was filled with the capsule.  Five milliliters of the sample were taken out at intervals of two, four, six, eight, ten, and twelve hours.  After every sampling, 5 ml of the dissolving medium is replaced, bringing the total volume of the dissolution fluid to 900 ml.  Six capsules were used in the release studies, and the mean values were displayed against time.  Using a twin beam UV and visible spectrophotometer, each sample was examined at 234 nm in comparison to a reagent blank.  A standard calibration curve was used to determine the medication concentration.

RESULT AND DISCUSSION

Physicochemical characterization of Blepharis repens polymer:

Table No: 1. physicochemical characterization of Blepharis repens polymer:

Phytochemical test

Using the appropriate reagents, phytochemical tests for alkaloids, glycosides, tannins, saponins, and flavonoids were conducted.   The initial test for alkaloids was conducted using Dragendoff's, Mayer's, Wager's, and Hager's reagents, which show that the BR polymer is devoid of alkaloids. To identify glycosides Tests for foaming were conducted.  The presence of glycosides is indicated by the persistent froth that was seen.  To identify tannins. When ferric chloride was used, no deep blue-black color was seen, indicating that tannins were not present.  Saponins are tested using photochemistry.  A foaming test was conducted.  The presence of saponins is indicated by the persistent froth that was seen.  To find flavonoids a lead acetate test was conducted.  Add a tiny amount of lead acetate to the BR solution.  The presence of flavonoids was indicated by the yellow-colored ppt that was seen.

UV- Analysis:

Plotting the absorbance of the standard solution against its concentration at λmax 225 nm yielded the standard calibration curve for the BR polymer.  The linear curve in the BR polymer standard solution had a correlation value of 0.981.  At a chosen λmax, their equation of line was y=0.002x+0.002. Plotting the absorbance of the standard solution against its concentration at λmax 225 nm yielded the standard calibration curve for paliperidone.  With a correlation coefficient of 0.98, the BR polymer's standard solution displayed a linear curve.  At a certain λmax, their equation of line was y=0.098x-0.000.

Micrometrics properties of pellets

The bulkiness of a formulation is measured by its bulk density and tab density.  Due to the spherical shape of the pellets, the results show no discernible difference between the two densities.  Excellent flow properties were obtained when the angle of repose was between 15 and 24 degrees.  The Carr's Index, or compressibility index, ranges from 3 to 13.

Testing the friability of pellets

The formulation of the pellets was determined to be friable between 0% and 0.5%.  All batches were determined to pass the friability test, with a maximum allowable level of 0.6%

In- vitro Dissolution Study

The sustained release capsule of metformin hydrochloride was the subject of 14-hour in vitro drug release research.  The sustained release behavior of each batch was examined in accordance with the experimental design specifications.  Because of the varying content of the capsule, the percent release was found to be significantly varied, ranging from 52.14 percent to 91.34%.

Table No: 2. Optimized composition of Metformin Hydrochloride Capsule with Blepharis repens polymer

Table No: 3. Pre-compression parameter of factorial design formulations

Table No: 4. Post compression parameters of Metformin Hydrochloride Capsule

Table No: 5. Post compression parameters of Metformin Hydrochloride Capsule