(T1430-07-42) Preparation and Characterization of Orally Disintegrating Tablets of Caffeine, Verapamil and Atenolol

Purpose: Oral disintegrating tablets (ODTs) are preferred alternative to conventional solid oral dosage forms. ODTs are intended to be placed in the mouth and anticipated to either dissolve or disperse when it comes in contact with the saliva. ODTs show rapid absorption, improved bioavailability, avoidance of first pass metabolism and are easy to administer, thus better patient compliance [1,2]. Three model drugs – Caffeine, Verapamil and Atenolol possessing diverse physicochemical properties are selected for the study. Caffeine is a neutral hydrophilic drug and belongs to BCS Class I. Verapamil is a basic lipophilic drug which belongs to BCS Class II. Atenolol is a basic hydrophilic drug that belongs to BCS Class III. The objective of the study is to formulate and characterize the orally disintegrating tablets of above-mentioned model drugs.

Methods: Tablets were prepared by sieving API, and excipients such as diluent, binder, disintegrant through sieve no. 20 and mixing in a V-blender at 25 rpm for 15 minutes. Lubricant was sieved through sieve no. 40 and was added to the mixture in a V-blender and blended at 25 rpm for 3 minutes. Mannitol was used as a diluent, Microcrystalline cellulose pH 101 as a binder, Croscarmellose sodium as a disintegrant and Magnesium stearate as a lubricant. The mixture was passed through roller compactor (TFC-Lab Micro Roller compactor) to obtain roller compacted sheets. These sheets were granulated through sieve no. 20 using oscillator granulator to get dry granules. Dry granules were mixed with extra granular materials such as sweetener, flavoring agent, disintegrant and lubricant. Aspartame and Acesulfame potassium are used as sweeteners and peppermint as flavoring agent. The mixture is then compressed into tablets using tablet compression machine Acura Mini Rotatory Tablet Press using 9.5mm, round, S/C B tools. Tablets were analyzed for weight variation, thickness, hardness, friability, disintegration, assay, content uniformity of dosage units (atenolol only) and in-vitro dissolution. Thickness was measured by using vernier calipers and hardness by using Pharmatron 6D - Tablet hardness tester. Friability was measured by using VANDERKAMP 10809 Friabilator Counter. The disintegration time was measured in vitro using US pharmacopeia monograph method. Dissolution was measured in-vitro using US pharmacopeia monograph method. Both assay and dissolution samples were measured using HPLC.

Results: Prepared tablets have weight variation, thickness, hardness, and average drug content within the pharmacopoeia limits.[4] All tablets showed acceptable friability ( < 1%). Caffeine, verapamil, and atenolol tablets have hardness 6.67 ± 0.51, 7.90 ± 0.8, and 7.17 ± 1.24 correspondingly. In-vitro disintegration time varies from 42 ± 9.70 secs, 25 ± < 2 secs, and 1.24 ± 0.13 mins for caffeine, verapamil, and atenolol tablets respectively. In-vitro dissolution test showed 97.74 ± 4.76%, 95.81 ± 2.62 %, and 94.55 ± 1.70% drug released at 15 mins for caffeine, verapamil, and atenolol tablets, respectively. The evaluation results showed tablets have excellent hardness, short disintegration time and more than 90% in-vitro drug dissolution at 15 mins.

Conclusion: ODTs prepared using dry granulation method followed by compression have good compressibility. Friability and disintegration time are within the pharmacopeial limits.  More than 90% of the drug is released within 15 minutes, showing the feasibility of this approach for preparing ODTs.

References: 1. Porter, Stuart C. "Novel drug delivery: Review of recent trends with oral solid dosage forms." American Pharmaceutical Review 4 (2001): 28-36.
2. AlHusban, Farhan, et al. "Recent patents and trends in orally disintegrating tablets." Recent Patents on Drug Delivery & Formulation 4.3 (2010): 178-197.
3. United States Food and Drug Administration. Orally disintegrating tablets. Guidance for industry. Rockville. Maryland: FDA; 2008.

Characterization of orally disintegrating tablets of Caffeine, Verapamil and Atenolol