Formulation And In-Vitro Evaluation of Sustained Release Matrix Tablets of Telmisartan Using Various Hydrophilic Polymers

Elevated blood pressure is the hallmark of hypertension, a chronic illness that can cause serious cardiovascular problems if unchecked. Angiotensin II receptor blockers (ARBs), such as telmisartan, are frequently given to treat hypertension and lower the risk of cardiovascular disease. However, Telmisartan has drawbacks that can result in fluctuating plasma concentrations and decreased therapeutic efficacy, including poor aqueous solubility, variable absorption, and a very extended half-life. Sustained release (SR) drug delivery systems were created to get around these restrictions by giving the medication a steady, regulated release over a long period of time. These systems provide a number of benefits, such as increased patient compliance, decreased dosage frequency, and enhanced therapeutic efficacy. Telmisartan sustained release tablets are being developed with the goals of preserving an optimal plasma medication concentration, reducing adverse effects, and improving patient compliance with treatment plans. In this work, hydrophilic polymers such hydroxypropyl methylcellulose (HPMC) and ethyl cellulose were used in an effort to manufacture and assess sustained release matrix tablets of telmisartan. To guarantee the intended release profile, the tablets were made using the direct compression method and assessed for a number of physicochemical characteristics as well as in vitro drug release behavior. Particularly when taking into account the mortality, diminished quality of life, and disability linked to cardiovascular disease and stroke, hypertension clearly has a detrimental impact on health. In 2019, 92 million disability life-years (6% of total) and 7.6 million deaths (13.5 percent of all deaths) were caused by systolic blood pressure that was higher than the 115 mmHg threshold. Finding out that a preventable cause is responsible for such pervasive negative effects is depressing. The oral route has been the most widely used method of administering medication for the long-term treatment of numerous conditions. Using a hypertensive agent as a model medication candidate, the study's objective was to apply optimization to create the best bilayer tablet for antihypertensive patients. Combination medication therapy is recommended for the treatment of hypertension because it enables medications with different mechanisms of action to work in concert and successfully reduce blood pressure at dosages below each drug's maximum. The goal of any drug delivery system is to swiftly establish and then maintain the proper drug concentration by delivering a therapeutic dose of medication to the right location in the body. The two most important aspects of drug delivery are the dispersion of medication in space and time. Spatial location is necessary for drug targeting to a particular organ or tissue. Bilayer tablet technology is used to create immediate and sustained release formulations for a single medication or a combination of medications. In some situations, bilayer tablets are advantageous because they provide improved patient compliance by maintaining consistent drug levels, lowering dosage and adverse effects, and increasing the safety margin for high-potency medications. Amlodipine and Telmisartan are antihypertensive medications that work by inhibiting the effects of calcium channel blockers and angiotensin receptor blockers (ARBs). The complexation process has also been used to successfully increase the solubility and bioavailability of telmisartan by creating a nanocomposite of the drug with cyclodextrin (World Journal of Pharmaceutical Research 1122). There have been reports of telmisartan being released by the creation of a drug-Aminoclay complex, with the release being reliant on the medium's pH. For all of the produced formulations, telmisartan demonstrated improved bioavailability and rapid dissolution from these complexes at pH 1.2. There have also been reports of the formulation and assessment of pH-modulated solid dispersions using a variety of telmisartan solubilization techniques. However, a long-lasting medication impact that can sustain the drug's concentration in the body for an extended length of time is necessary for the treatment of hypertension. The telmisartan tablets that are now on the market are traditional tablets that only release the medication for a few hours. Since telmisartan dissolves and takes effect quickly, it is not appropriate to make it available for immediate release.

Drug Profile:

MATERIALS AND METHODS:

Telmisartan – Active pharmaceutical ingredient (API), obtained as a gift sample or purchased from a certified supplier.

Hydroxypropyl Methylcellulose (HPMC K100M) – Sustained release polymer.

Ethyl Cellulose (EC) – Hydrophobic polymer used for controlled release.

Microcrystalline Cellulose (MCC) – Diluent to enhance compressibility.

Magnesium Stearate – Lubricant to prevent sticking during compression.

Talc – Glidant to improve powder flow properties.

Lactose Monohydrate – Filler or diluent (if needed)

Method of Preparation:

The following process was used to prepare the table using the wet granulation method. Table 1 lists the ingredients of the various SR pill formulations. In a planetary mixer, HPMC polymer, medication, and PVP were combined for five minutes. The powders were ground into granules, sieved through a 20 mesh screen, dried for one hour at 30 oC, then combined with magnesium stearate and talc. Using a tablet punching machine (Cadmach, Mumbai, India), the prepared granules were compacted into 150 mg tablets with an average hardness of 7 kg/cm2. The tablet formulations F1, F2, and F3 were given names.

Table 1: Composition of Various Formulations of Telmisartan Using HPMC and PVP

Pre-compressional Parameter

1)  Bulk density

It is the proportion of the powder's bulk volume to its overall mass. The weighed powder (after passing through a standard sieve #20) was poured into a measuring cylinder, and the initial volume was recorded. The bulk volume is the name given to this starting volume. From this, the bulk density is computed using the following formula. It is given by and expressed in g/cc:

Db = M/Vo

Where, M = mass of powder.

            V0 = the bulk volume of the powder.

2) Tapped Density

It is the proportion of the powder's total mass to its tapped volume. The powder was tapped 500 times to determine the volume. The tapped volume (the difference between these two volumes should be less than 2 percent) was then recorded after the tapping was completed 750 times. Tapping is repeated 1250 times and the tapped volume is recorded if it exceeds 2%. It is provided by and expressed in g/cc:

Dt = M/V1

Where, M = mass of powder.

            Vt = tapped volume of the powder.

3) Carr’s index (%)

The bulk density is calculated by dividing the sample's weight by its volume. The weight of the sample divided by the volume after 500 taps of the measuring cylinder from a height of 2 inches is known as the "tapped density." Carr's index, or the percentage compressibility, was computed as 100 times the ratio of the tapped density to the difference between the bulk and tapped densities.

4) Hausner’s ratio

Hausner’s ratio is the ratio of tapped density to bulk density. Lower the value of Hausner’s ratio better is the flow property.

Hausner’s Ratio = Bulk Density

5) Angle of Repose

The funnel method was used to calculate the mixes' angle of repose. The precisely weighed mixture was transferred into a funnel. The funnel's height was set so that the tip of the funnel barely touched the top of the mixture pile. The mixture was left to run off the surface of the funnel. The heap made from the blend was measured for height and diameter. The following formula was used to get the angle of repose.

Tan ? = h/r

 Where, H = height of the heap.

              R = radius of the heap of granules.

Fig: comparison of in vitro drug released profile of telmisartan tablet.