INTRODUCTION:

The concept of Fast dissolving Drug Delivery System emerged from the desire to provide patient with more conventional means of taking their medication. It is difficult for many patients to swallow tablets and hard gelatin capsules. Hence they do not comply with prescription, which results in high incidence of non-compliance and ineffective therapy¹. In some cases such as motion sickness, sudden episodes of allergic attacks or coughing and unavailability of water, swallowing conventional tablets may be difficult². Particularly the difficulty is experienced by pediatric and geriatric patients but it is applicable to people who are ill in bed and those active working patients who are busy or traveling, mentally ill, developmentally disable and patients who are uncooperative. To overcome this problem fast dissolving tablet is prepared³. Such problems can be resolved by means of Fast Dissolving Tablet. When put on tongue, this tablet disintegrates instantaneously, releasing the drug, which dissolves or disperses in the saliva. Some drugs are absorbed from the mouth, pharynx and esophagus as the saliva passes down into the stomach. In such cases, bioavailability of drug is significantly greater than those observed from conventional tablet dosage form⁴.

Superdisintegrants added in the formulation increase the dissolution characteristics thus increasing the bioavability of drug⁵. Telmisartan is a nonpeptide Angiotensin Receptor ΙΙ (Type- ATΙ) Antagonist, That Cause Inhibition Of the action of Angiotensin II on Vascular Smooth Muscle in the Symptomatic Treatment of Hypertension. In the present an attempt has been made to develop fast dissolving tablets of telmisartan by direct compression method using three different disintegrant in different concentrations and meglumine as organic base. Meglumine is chemically 1-Deoxy-1-(methylamino)-D-glucitol an organic base used as a pH-adjusting agent. So, it converts acidic pH to basic. It increases absorption of telmisartan in the stomach as well as in the intestine. Hence, the objective of the present study demonstrated that the melumine buffer is rapidly increases the pH in the stomach and it increases the absorption of telmisartan.

MATERIAL AND METHODS:

Materials:

Telmisartan is procured by Alembic research centre, Baroda. Crosscaromellose Sodium, Sodium starch glycolate and Crosspovidone are gifted by Maruti Chemicals, Ahmedabad. All other ingredients used were of analytical grade.

Methods:

Preparation of fast dissolving telmisartan tablets (Table-1):

Telmisartan fast dissolving tablets were prepared by direct compression method using variable concentration of disintegrants like croscarmellose sodium, crosspovidone, sodium starch glycolate. Pearlitol SD200, micro crystalline cellulose, meglumine, PVP K30, aspartame were sifted through #60. Telmisartan was geometrically sifted through #40. The entire ingredients were blended uniformly. Magnesium stearate passed through #60 and lubricate the material. The resulting lubricated material was compressed into tablet with 8.0 mm punches.

Evaluation of granules:

The angle of repose was measured by using funnel method, which indicates the flowability of the granules. Loose bulk density (LBD) and tapped bulk density (TBD) were measured using the formula: LBD= weight of the powder/volume of the packing. TBD= weight of the powder/tapped volume of the packing. Compressibility index of the granules was determined by using the formula: CI (%) = [(TBD-LBD/TBD)] ×100. The physical properties of granules were shown in Table 2-3.^6,7

Evaluation of tablets:

Thickness:

Thickness of tablets was determined using Vernier caliper. Five tablets from each batch were used and an average value was calculated⁸.

Hardness:

The tablet hardness, which is the force required to break a tablet in a diametric compression force. The hardness tester used in the study was Monsanto hardness tester, which applies force to the tablet diametrically with the help of an inbuilt spring⁸.

Friability:

The friability of a sample of 20 tablets was measured using Roche friabilator (Electrolab, Mumbai, India). Twenty tablets were weighed, rotated at 25 rpm for 4 minutes. Tablets were reweighed after removal of fines (dedusted) and the percentage of weight loss was calculated. Friability below 1% was considered acceptable⁸.

Wetting Time:

A piece of tissue paper folded double was placed in a Petri plate containing 6ml of water. The tablet was placed on the paper and the time for complete wetting of the tablet was measured in seconds^9,10.

In vitro disintegration time:

The disintegration time of the tablet was measured in water (37 ± 2°C) according to disintegration test apparatus with disk. The time in seconds taken for the complete disintegration of the tablet with no palpable mass in the apparatus was measured in seconds. Three tablets from each batch (formulation) were tested for the disintegration time calculations⁸.

In vitro dissolution Studies:

In vitro drug release studies for the fast dissolving of telmisartan was studied using dissolution test apparatus II USP XXII model [Paddle type] for the fabricated batches with the rotation speed of 75 rpm using phosphate buffer pH 7.5 as the dissolution medium maintained at a temperature of 37 ± 0.5ºC. Samples were withdrawn at predetermined time interval and filtered through Whatman filter paper, diluted suitably and analyzed at 296 nm for cumulative drug release using Schimadzu UV-Visible spectrophotometer. The dissolution experiments were conducted in triplicate.

Stability studies:

The optimized formulation was subjected to stability study at 40 ± 2ºC and 75 ± 5% RH for 90 days. The samples were withdrawn at intervals of fifteen days and checked for physical changes, hardness, friability, drug content and percentage drug release¹¹.

RESULTS AND DISCUSSION:

FTIR spectroscopy:

The pure drug telmisartan, superdisintegrants and various excipients used in the preparation of fast dissolving tablet formulations were characterized by FT-IR spectroscopy to know the compatibility. As shown in figure 1-8, there was no significant difference in the FT-IR spectra of pure telmisartan, drug along with superdisintegrants and optimized formulation.

Characterization of powder blend:

Granules prepared for compression of fast dissolving tablets were evaluated for their flow properties, the results were shown in Tables 2-3. Angle of repose was in the range of 33.14 ± 0.15º to 28.52 ± 0.14º which indicates excellent flow of the powder for all formulations. The bulk density of the powder formulation was in the range of 0.509 ± 0.62 to 0.531 ± 0.12 gm/ml; the tapped density was in the range of 0.610 ± 0.21 to 0.623 ± 0.19 gm/ml, which indicates that the powder was not bulky. The Carr’s index was found to be in the range of 14.98 to 16.69% indicating compressibility of the tablet blend is good. These values indicate that the prepared powdered exhibited good flow properties.

Physicochemical evaluation of fast dissolving tablets:

The fast dissolving telmisartan tablets were white, smooth and round shaped in appearance. The results of physicochemical characterizations are shown in Tables 4-5. The thickness of fast dissolving tablets were measured by vernier caliper and were ranged between 4.33 ± 0.12 and 4.37 ± 0.23 mm. Weight variation for different formulations were found to be 245 ± 1.093 to 255 ± 1.485 mg, showing satisfactory results as per Indian Pharmacopoeia (IP) limit. The hardness of the fast dissolving tablets was measured by Monsanto tester and was controlled between 35 and 41 N. The friability was below 1% for all the formulations, which is an indication of good mechanical resistance of the tablet. The percentage of drug content for F1 to F6 was found to be in between 98.1 ± 0.11 to 99.0 ± 0.22 of telmisartan it complies with official specifications.

Table-1: Preparation of fast dissolving telmisartan tablets formulations

Sr. No	Ingredients (mg/tablet)	Batch No.
	Ingredients (mg/tablet)	F1	F2	F3	F4	F5	F6	F7	F8	F9	F10 10
	Disintegrants Concentration	1:2	2:1	1.5:1.5	1.5:1.5	1.5:1.5	2	4	3	3	3
1	Telmisartan	40	40	40	40	40	40	40	40	40	40
2	Pearlitol SD200	85.5	85.5	85.5	85.5	85.5	85.5	85.5	85.5	85.5	85.5
3	MCC	102	102	102	102	102	104.5	99.5	102	102	102
4	Meglumine	3	3	3	3	3	3	3	3	3	3
5	PVP K30	4	4	4	4	4	4	4	4	4	4
6	Crospovidone	2.5	5	3.75	-	3.75	5	10	7.5	-	-
7	Sodium starch glycolate	5	2.5	3.75	3.75	-	-	-	-	7.5	-
8	Cross carmellose sodium	-	-	-	3.75	3.75	-	-	-	-	7.5
9	Aspartame	5	5	5	5	5	5	5	5	5	5
10	Magnesium stearate	3	3	3	3	3	3	3	3	3	3
Total Weight		250	250	250	250	250	250	250	250	250	250

Table 2: Granules properties of formulations F1 to F5 of telmisartan fast dissolving tablets

Formulation Code	Parameters
Formulation Code	F1	F2	F3	F4	F5
Angle of repose (θ)	30.24± 0.08	31.25± 0.18	30.75± 0.06	32.12± 0.14		31.07± 0.39
Loose bulk density (LBD) (g/ml)	0.509±0.62	0.517±0.14	0.514±0.14	0.524±0.22		0.531±0.12
Tapped bulk density (TBD) (g/ml)	0.611±0.21	0.612±0.11	0.611±0.12	0.621±0.18		0.623± 0.19
Compressibility index (%)	16.69±0.25	15.52±0.41	15.88±0.42	15.62±0.36		15.45±0.28

Table 3: Granules properties of formulations F6 to F10 of telmisartan fast dissolving tablets

Formulation Code	Parameters
Formulation Code	F6	F7	F8	F9	F10
Angle of repose (θ)	33.14± 0.15	28.52± 0.14	27.14± 0.19	30.45± 0.12	31.29± 0.15
Loose bulk density (LBD) (g/ml)	0.519±0.16	0.519±0.13	0.523±0.16	0.518±0.25	0.519±0.16
Tapped bulk density (TBD) (g/ml)	0.619±0.26	0.612±0.12	0.610±0.21	0.614±0.27	0.619±0.26
Compressibility index (%)	16.16±0.46	15.2±0.24	14.98±0.31	16.12±0.42	16.16±0.16

Table 4: Tablet properties of formulations F1 to F5 of telmisartan fast dissolving tablets.

Formulation Code	Parameters
Formulation Code	F1		F2	F3	F4	F5
Thickness (mm)		4.35± 0.19	4.33± 0.12	4.36± 0.15	4.34± 0.13	4.37± 0.23
Hardness (N)		39	35	37	41	40
Friability (%)		0.56	0.54	0.62	0.61	0.58
Drug content (%) Disintegration time (sec) Wetting time (sec)		98.1 ± 0.11 30 74	98.2 ± 0.41 35 69	99.0 ± 0.22 36 64	98.6± 0.31 32 72	98.1 ± 0.25 39 65

Table 5: Tablet properties of formulations F6 to F10 of telmisartan fast dissolving tablets.

Formulation Code	Parameters
Formulation Code	F6	F7	F8	F9	F10
Thickness (mm)	4.34± 0.12	4.38± 0.22	4.36± 0.16	4.35± 0.28	4.34± 0.20
Hardness (N)	36	40	36	35	39
Friability (%)	0.57	0.63	0.60	0.55	0.59
Drug content (%) Disintegration time (sec) Wetting time (sec)	98.6 ± 0.16 45 78	98.3 ± 0.14 34 85	99.5 ± 0.24 25 58	98.2 ± 0.10 28 71	98.2 ± 0.15 29 79

Table 6: Percentage drug release of formulations F-1 to F-10

Time in min.	Formulations
Time in min.	F-1	F-2	F-3	F-4	F-5	F-6	F-7	F-8	F-9	F-10
0	0	0	0	0	0	0	0	0	0	0
2	45.28	42.90	42.44	42.90	40.51	42.90	46.18	55.29	48.34	37.59
4	50.05	47.66	51.26	53.76	45.79	46.24	51.75	60.48	55.14	48.59
6	57.20	52.43	59.58	57.20	51.76	54.81	56.59	69.75	56.29	58.19
8	69.12	64.35	68.48	65.14	54.81	61.24	64.29	81.96	62.37	59.36
10	73.88	71.50	76.27	68.19	57.83	67.17	75.78	88.48	74.51	65.34
15	83.42	76.27	78.65	72.50	72.69	74.76	82.36	95.67	84.29	72.49
20	88.18	83.42	83.42	73.81	75.63	79.98	86.43	96.17	86.49	74.25
25	90.57	85.80	85.80	76.27	76.51	80.49	87.21	96.73	90.76	74.98
30	90.89	85.91	86.89	77.49	78.43	81.39	88.49	97.19	90.99	75.48