Optimization and Formulation of Orodispersible Tablets of ...

1 Singh & Singh Tropical Journal of Pharmaceutical Research, April 2009; 8 (2): 153-159. Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria.. All rights reserved Available online at Research Article Optimization and Formulation of Orodispersible Tablets of Meloxicam Jashanjit Singh1* and Rajmeet Singh2. 1 2. Department of Pharmaceutics, Swift School of Pharmacy, Village- Gaagar Sarai,Rajpura, Department of Pharmaceutics ,GHG Khalsa College of Pharmacy, Guru Sar Sadhar, Ludhiana,Punjab, India. Abstract Purpose: The objective of this study was to formulate and optimize an Orodispersible 2. Formulation of meloxicam using a 2 factorial design for enhanced bioavailability. Methods: The Tablets were made by non-aqueous wet granulation using crospovidone and 2. mannitol.

2 A 2 factorial design was used to investigate the amount of crospovidone and taste masking, soothening hydrophilic agent (mannitol), as independent variables, and disintegration time as dependent response. Formulated Orodispersible Tablets were evaluated for weight variation, friability, disintegration time, drug content, wetting time, water absorption ratio and in vitro drug release. Results: The results show that the presence of a superdisintegrant and mannitol is desirable for orodispersion. All the formulations satisfied the limits of orodispersion with a dispersion time of less than 60 sec. For example, Formulation F4 showed a disintegration time of 2. sec, crushing strength of kg/cm , drug content of and fast drug release rate of within 30 min, as compared with the conventional tablet ( ) . Conclusion: It is feasible to formulate Orodispersible Tablets of meloxican with acceptable disintegration time, rapid drug release and good hardness, which could be amenable to replication on an industrial scale.

3 Keywords: Meloxicam, Orodispersion, Crosspovidone, Mannitol, Factorial design, Tablet properties. Received: 29 September 2008 Revised accepted: 28 December 2008. *Corresponding author: E-mail- Tel no.: +91-9814819282, +91-1762-653496 Fax +91-175-2300711. Trop J Pharm Res, April 2009; 8 (2): 153. Singh & Singh Introduction Methods Difficulty in swallowing is a common problem Experimental design of all age groups, especially geriatric and 2 6. pediatric patients, due to physiological The 2 factorial design was implemented for changes associated with these groups. These the Optimization of meloxicam Orodispersible problems can be solved by development of a tablet. The dependent response measured novel type of solid dosage form, namely, was disintegration time. Two independent Orodispersible tablet, which disintegrates and factors - the concentration of crospovidone dissolves rapidly in saliva without the need of and concentration of mannitol - were set at swallowing with drinking water since the tablet two different levels.

4 High and low levels of is placed in the mouth where it disperses each factor were coded +1 and 1, 1,2. rapidly before swallowing . respectively (Table 1). 2. Clinically, nonsteroidal anti-inflammatory Table 1: Experimental design 2 used for drugs (NSAIDs) are the most frequently Optimization of Orodispersible Tablets prescribed by physicians for inflammatory disorders. Meloxicam [4-hydroxy-2methyl-N- Formulation Crospovidone Mannitol (5-methyl-2-thiazolyl)-2H-1,2-benzothiaz ine-3- (%w/w) (%w/w). carboxamide1,1-dioxide], a nonsteroidal anti- F1 2 30. inflammatory drug, was chosen as a model F2 5 30. F3 2 44. drug for this study. It is one of the most F4 5 44. commonly prescribed NSAIDs for the treatment of various inflammatory conditions Preparation of meloxicam Tablets such as rheumatoid arthritis, osteoarthritis, 3.

5 Low back pain . Although, it has excellent Orodispersible Tablets of meloxicam were 4. bioavailability (89%) , its poor aqueous prepared as per the formula given in Table 2. 5. solubility makes absorption and dissolution Accurately weighed quantities of meloxicam, rate-limited, thus delaying onset of action. mannitol, crospovidone and other excipients Consequently, an Orodispersible Formulation were passed through sieve number 10 (as per 7. of meloxicam was developed that could Indian Pharmacopoeia) and mixed in a glass enhance the bioavailability and extent of mortar. The above blend was granulated with bioabsorption of the drug. a non-aqueous granulating agent, alcoholic solution of PVP (10%w/v), and passed Experimental through a sieve of aperture size, 710 m. The granules were air-dried, mixed with 2%w/w Materials colloidal silicone dioxide, and the granules were passed through sieve number 22, (as 7.)

6 Meloxicam was obtained from Siemen per Indian Pharmacopoeia) lubricated with Laboratories, Haryana, India while magnesium stearate and compressed using Crosspovidone was supplied by Signet CADMACH SMS25 single punch tablet machine at a fixed compression force of 400. Chemicals, Mumbai, India. Mannitol, colloidal kgf . The mean weight and diameter of the silicone dioxide and spray dried lactose were Tablets were 100mg and 8mm, respectively. obtained from Ranbaxy Fine Chemicals Ltd, New Delhi, India. Sodium saccharine and Evaluation of Orodispersible tablet magnesium stearate were obtained from Fine Chemicals, Mumbai, India. All other All the Tablets were evaluated for the following solvents used were of analytical grade. parameters: Trop J Pharm Res, April 2009; 8 (2): 154. Singh & Singh Table 2: Composition of Orodispersible Tablets of meloxicam Formulations Ingredients(mg/tablet).

7 F1 F2 F3 F4. Meloxicam Crospovidone* 2 5 2 5. Mannitol* 30 30 44 44. Sodium saccharine 1 1 1 1. Colloidal silicone dioxide 2 2 2 2. Magnesium stearate 1 1 1 1. Spray dried lactose *As per experimental design. Weight variation hardness (crushing strength) of three Tablets per batch was determined and mean taken. Twenty Tablets were randomly selected from each batch and individually weighed. The Percentage drug content average weight of these selected Tablets was calculated. Drug content was determined by taking randomly ten Tablets per batch. An amount Friability equivalent to 10 mg meloxicam was dissolved 8. Tablet friability was measured using a in methanol, suitably diluted with HCL. ROCHE friabilator (USP) at 25 rpm for 4 min. and filtered. The absorbance of the solution The weight of twenty Tablets before and after was measured spectrophotometrically against completion of the test was recorded and the blank ( N HCl) at 354 nm using a friability was calculated by the following (Shimazdu-1700, formula: Japan).

8 Percentage friability= (initial weight-final weight/initial weight) 100 (1) Kinetic digital images Disintegration time One tablet of the selected Formulation was placed in a glass full of water (see Figure 1). Three Tablets per batch were evaluated for and the dispersion process was recorded, disintegration time by employing a modified without agitation, and kinetic digital images 9. dissolution apparatus . Instead of the were taken with a mega pixel camera disintegration apparatus described in JP XII, a (Sony- DSC-W55, Japan). modified dissolution apparatus (JP XII paddle method) was employed. Water (900 ml), Wetting time and water absorption ratio 0. maintained at 37 C was stirred with a The wetting time of the tablet was measured paddle at 100 rpm. Disintegration time was by placing five circular tissue papers (10 cm in recorded when all the fragments of the diameter) in a Petri dish of 10 cm diameter.

9 Disintegrated tablet passed through the screen Water (10 ml) containing methylene blue of the basket. ( w/v) was added to the Petri dish. A. tablet was carefully placed on the surface of Crushing strength the tissue paper and the time required for the Tablet crushing strength, which is the force dye to reach the upper surface of the tablet required to break the tablet, was measured was recorded as wetting time. The measure- with a Pfizer tablet hardness tester. The ments were carried out in triplicate. Water Trop J Pharm Res, April 2009; 8 (2): 155. Singh & Singh was selected. A two-level experimental design provides sufficient data to fit a polynomial 11. equation (Eq. 3) which is in the following form: y = B0 + B1X1 + B2X2 + B12(X1X2) (3). where y represents the experimental response, B0 the intercept and B1 to B12 are the coefficients for the factors X1.

10 (crospovidone) and X2 (mannitol). Students t- test was employed to examine the probability Figure 1: Sequential disintegration of orodisper- of each coefficient being equal to zero. All sible Tablets of meloxicam (A = 0 sec; B = 5 sec; C tests were performed at a 95% confidence = 10sec; D = 15sec; E = 20 sec; F = 25 sec; G = 30. sec; H = 40 sec) level (P> ). In the final model equation, only the significant factors were included. The absorption ratio was calculated using Eq. 2. 10. : polynomial equation was applied to the response parameter, disintegration time, using Water absorption ratio = (W a W b)/ W b .. (2) a software (New Statistica 10v, USA). where W b = weight of tablet before absorption Results of water , and W a = weight of tablet after absorption of water. The results of the measurements of various tablet parameters are tabulated in Table 3.