FORMULATION AND EVALUATION OF ORODISPERSIBLE TABLETS OF PERINDOPRIL ERBUMINE USING NATURAL SUPERDISINTEGRANT

: Oral disintegrating tablets are emerging trend in Novel drug delivery system & received increasing demand & popularity due to ease of administration & better patient compliance .In recent years superdisintegrant have been employed to develop effectual mouth dissolving tablet & to overcome limitation of conventional tablets .In present study attempt was made to compare to disintegrating efficiency of natural superdisintegrats .Main aim of using oscimum basilicum as natural superdisintegrant was to achieve quick onset of action ,increases water uptake with short wetting time & decreasing disintegration time by cost effective direct compression method. 3 preliminary batches were prepared & these are evaluated for precompression parameter like angle of repose, carr`s index & post compression parameters like wetting time, water absorption ratio,in vitro disintegration. Hardness, friability of all formulations found within limit. Best formulation F2 batch had shown good hardness, friability, disintegration time, swelling time. Present study revealed that mucilage obtained from oscimum basilicum was effective for their disintegrating property.

used were of Analytical grade & distilled water was used throughout the work.

Direct
Compression Method: Excipients like mannitol,talc,microcrystalline cellulose were passed through sieve.Magnesium stearate used for lubrication purpose.

Extraction of mucilage from Oscimum Basilicum 4-7 :
1) Oscimum basilicum plant was procured from the local nursery and the seeds were separated from same. 2) To it we added the alkali &heated it.
3) Rinsed it with water. 4) Soaked it for 6 to 7 hours. Separated out mucilage & discarded the seed coat& cotyledon. 5) As the mucilage contains the water it was dried until it became completely free from moisture. 6) It was Grind & used as dry powder.

Preformulation Studies:
Solubility Studies Solvents like distilled water & ethanol were used for solubility determination of Perindopril Erbumine.
Identification of Pure Drug FTIR spectroscopy was used for identification of pure drug.
Melting Point Determination Determination of melting point was done by capillary method.

Determination of λmax
Preparation of Stock Solution: An accurately weighed 10 mg of Perindopril Erbumine was transferred in a 100ml volumetric flask. To the flask phosphate buffer was added in small proportion so as to dissolve Perindopril Erbumine. The volume was made up to 100ml with

ABSTRACT:
Oral disintegrating tablets are emerging trend in Novel drug delivery system & received increasing demand & popularity due to ease of administration & better patient compliance .In recent years superdisintegrant have been employed to develop effectual mouth dissolving tablet & to overcome limitation of conventional tablets .In present study attempt was made to compare to disintegrating efficiency of natural superdisintegrats .Main aim of using oscimum basilicum as natural superdisintegrant was to achieve quick onset of action ,increases water uptake with short wetting time & decreasing disintegration time by cost effective direct compression method. 3 preliminary batches were prepared & these are evaluated for precompression parameter like angle of repose, carr`s index & post compression parameters like wetting time, water absorption ratio,in vitro disintegration. Hardness, friability of all formulations found within limit. Best formulation F2 batch had shown good hardness, friability, disintegration time, swelling time. Present study revealed that mucilage obtained from oscimum basilicum was effective for their disintegrating property. Keywords: Direct Compression, ODTs, Natural Superdisintegrant Ocimum basilicum brought to you by CORE View metadata, citation and similar papers at core.ac.uk Determination of λ max: 20μg/ml solution of Perindopril Erbumine was prepared in diluent. The resulting solution was scanned in UV-Vis spectrophotometer from 400-200nm to determine the λmax. The λmax of Perindopril Erbumine was found to be 215 nm.

Preparation of Calibration Curve for Perindopril
Erbumine: Aliquots (0.2-2.0ml) from standard stock solution were pipetted out in series of ten 10 ml volumetric flask and the volume was made up with phosphate buffer. The absorbance was measured in triplicate at 215 nm against blank.

Fourier Transform Infrared Spectroscopy (FTIR):
The drug was subjected to IR spectroscopy using FT-IR (SHIMADZU 8400S) and the KBr disk method.

Preparation of Batches of Orodispersible Tablets of Perindopril Erbumine:
For formulating orodispersible tablets Drug, mannitol. Magnesium stearate, talc, natural superdisintegrant (Ocimum basilicum) were used. Mannitol was used as diluents and imparts cooling sensation in Mouth. Microcrystalline cellulose was used as binder. The concentrations of Oscimum basilicum was varied between2.5% to 5 %. All ingredients were passed through mesh 250 μm for preparation of granules. The ingredients were mixed according to batches. Magnesium stearate and talc were added in a final step and mixed. This mixture was subjected for evaluation of pre compression parameters which included Angle of repose, Bulk density, Tap density, Carr's index and Hausner's ratio & after that it was compressed on 8 mm (diameter) flat punches on a 'Rimek mini press 16 station rotary compression machine. Each tablet weighing 200 mg corresponding to 4 mg of Perindopril Erbumine were obtained. The prepared tablets were evaluated for wetting time, weight variation, thickness, friability, hardness and in-vitro disintegration time, In-vitro dissolution time.

Evaluation of precompression parameters
Precompression Parameters:

Angle of Repose (θ):
Angle of repose is defined as the maximum angle possible between the surface of a pile of the Powder and horizontal plane. The frictional force in a loose powder or granules can be measured by angle of repose.

tan θ= h / r θ= tan-1 (h/r)
Where, θ is the angle of repose h is height of pile r is radius of the base of pile 2. Bulk Density: Bulk density is defined as the mass of a powder divided by the bulk volume. The bulk density of a powder depends primarily on particle size distribution, particle shape, and the tendency of the particles to adhere to one another.

Carr's Compressibility Index:
The compressibility index of the granules was determined by Carr's compressibility index.

4.Hausners Ratio:
It is determined by comparing tapped density to the bulk density by using following equation Hausners ratio= tapped density / bulk deksity.

Evaluation of Tablet properties:
Uniformity of Weight 8 The test was performed according to specifications given in the Ph. Eur., 2004 on 20 tablets. The maximum acceptable limit is ±7.5% deviation of an individual mass from average mass.

Measurement of Tablet Friability 9
Tablet friability was measured using the Roche Friabilator according to Ph. Eur, on ten tablets each. The friability was determined as the mass loss in percent according to Eq Where f-Friability, WA-Initial weight (g), WB-Final weight (g) Tablets of friabilities under 1% are acceptable.

Measurement of Tablet hardness: The crushing strength of tablets was measured by a Monsanto Hardness Tester
Wetting Time 10 : A piece of tissue paper was folded twice and placed in small petri dish containing 6 ml of phosphate buffer (pH 6.8) the tablet was placed on it and the time required for complete wetting of tablet was recorded.
Water Absorption Ratio 11 : A piece of tissue paper folded twice was placed in a small petri dish containing 6 ml of water. A tablet was put on the paper and was allowed for complete wetting. The wetted tablet was then weighed. Water absorption ratio, R, was determined using following equation

R= (WA-WB) /WB *100
Where, WB-Weight of tablet before water absorption, WA-Weight of tablet after water absorption In Vitro Disintegration Time (DT) Using Petri Dish Method: The in-vitro disintegration time of the orally disintegrating tablets was determined following the procedure described by Gohel et al (2004) 12 . 10 mL of water at 37 0 C was placed in a petri dish of 10 cm diameter. The tablet was then carefully positioned in the center of the petri dish and the time required for the tablet to completely disintegrate into fine particles was noted. Measurements were carried out in replicates of three tablet (n=3) and mean were recorded.
In Vitro Dissolution Study: Perindopril erbumine tablet test conditions for the dissolution rate studies were used according USP,specifications using USP 24, type II apparatus. The dissolution medium was 900 ml of Phosphate buffer (pH 6.8). The temperature of the dissolution medium and the rate of agitation were maintained at 37±0.5°C and 50 rpm, respectively. Aliquots of 5.0 ml of the dissolution medium were withdrawn at specific time intervals and the volume replaced by fresh dissolution medium, pre-warmed to 37±0.5°C. The drug concentration was determined spectrophotometrically at 215 nm using UV spectrophotometer (shimadzu 1800).

RESULT & DISCUSSION:
Preformulation studies:  Solubility studies: Perindopril was freely soluble in distilled water & ethanol after solubility determination.  Melting point determination: After performing capillary method melting point of Perindopril found in range of 154-156 o C.  Standard calibration curve of Perindopril Erbumine: λ max was found to be at 215 nm, so the calibration curve of perindopril Erbumine was developed at this wavelength. The calibration curve showed linearity between 2-10 μg/ml concentration ranges. The standard calibration curve of Perindopril Erbumine was determined in phosphate buffer pH 6.8 by plotting absorbance against concentration at 215 nm the r 2 value was found to be 0.998. The calibration curve is presented in as follows: The powder flow properties were analyzed. It was observed that all formulations showed good flow properties with Carr's index ranging from 11.66 to 19.04 and Hauser's ratio below 1.25 which indicated good compressibility and flowability.

Evaluation of post compression parameters of preliminary batches of Perindopril:
The preliminary batches were evaluated for the post compression characteristics such as uniformity of weight, friability, hardness and In-Vitro Disintegration. The results of the evaluation are given in the following table. In vitro disintegration time: The disintegration time was measured, using a petri plate method as described above. It was found that tablets containing 2.5%, 3.75% and 5% of natural superdisintegrant showed disintegration time that was within 3 minutes. The basic principal that governs the action of superdisintegrant Oscimum basilicum is its extensive swelling which was found to increase with the increasing concentration of oscimumbasilicum above 3.75% as the contact of water with superdisintegrant led to formation of viscous plug. Due to increased viscosity with increased concentration of oscimumbasilicum it was observed that further uptake may be retarded and the tablets break into large particles instead of disintegrating into smaller particles.

% drug release:
Perindopril erbumine tablet test conditions for the dissolution rate studies were used according USP specifications using USP 24, type II apparatus. The dissolution medium was 900 ml of 0.1N Phosphate buffer. The temperature of the dissolution medium and the rate of agitation were maintained at 37±0.5°C and 50 rpm ,respectively. Aliquots of 5.0 ml of the dissolution medium were withdrawn at specific time intervals and the volume replaced by fresh dissolution medium, pre-warmed to 37±0.5°C. The drug concentration was determined spectrophotometrically at 215 nm using UV spectrophotometer (shimadzu 1800).   Average Wetting time of all 3 batches was obtained & found in range of1.44.. It was also observed that the batch F2 showed the wetting time of seconds which was less as compared to other batches.

Water absorption ratio:
It was observed due to water uptake & swelling behavier of natural superdisintegrant.It was observed that with increase in water absorption ratio the disintegration of tablets was faster as compared to the tablets with low water absorption ratio.F2 batch has good water absorption ratio.

In vitro disintegration time:
This was carried out as mentioned above. It was observed that F2 batch has least in vitro disintegration time with good wetting time, good water absorption ratio

CONCLUSION:
The rapid disintegrating tablets have potential advantages as compared to conventional dosage forms.Because of increased patient demand. Good bioavailability& rapid onset of action, these are expected to become more popular in today's leading World. Choice of drug Perindopril was associated with its ACE property. Ocimum basilicum plant was procured from the local nursery and the seeds were separated from same. Isolated Ocimum basilicum seeds mucilage was characterized on the basis of its organoleptic properties; micromeritic Properties (Angle of Repose, Bulk Density, Tapped Density, Compressibility Index, Hauser's Ratio).Along with melting point and solubility determination was also performed. In the present investigational study, it was concluded that mucilage obtained from natural superdisintegrant Ocimum basilicum showed better disintegrating property .So it was concluded that better results were obtained with F2 batch. Thus it can be concluded that Oscimum basilicum may be explored as high functionality excipient for future applications.