(T1330-12-82) Formulation and In Vitro Characterization of Orally Disintegrating Tablets of Drug Molecules with Varied Physicochemical Properties

Purpose: The aim of this study is to prepare and characterize orally disintegrating tablets with wide range of physicochemical properties. Subsequently, these oral disintegrating tables will be used to evaluate their pharmacokinetics and compare them with traditional oral tablets. Five model drugs – Caffeine, Verapamil, Atenolol, Propranolol, and Naproxen, with varying physicochemical properties are selected for the study.

Methods: The compatibility between the model drugs and the excipients was evaluated using differential scanning calorimetry (Seiko DSC6200/EXSTAR 6000) to select the excipients in formulations. The samples were analyzed with a nitrogen purge of 30 mL/min and a heating rate of 10 ºC/min, from 25 ºC to 500 ºC. The tablets were formulated by sieving model drug and excipients, including Mannitol (as a diluent), microcrystalline cellulose pH 101 (as a binder), sodium croscarmellose (as a disintegrant) through a No. 20 sieve. The mixture was blended in a V-blender at 25 rpm for 15 minutes. Magnesium stearate (as a lubricant) was sieved through No. 40 sieve and added to the mixture in the V-blender, followed by blending at 25 rpm for 3 minutes. The resulting mixture was then passed through a roller compactor (TFC-LAB MICRO ROLLER compactor) to obtain roller-compacted sheets. These sheets were further granulated by passing through No. 20 sieve using an oscillator granulator to obtain dry granules. After the dry granulation process, the granules obtained were blended with extra granular materials including Aspartame and Acesulfame K (as sweeteners), Peppermint (as a flavoring agent), Sodium croscarmellose (as a disintegrant), and Magnesium stearate (as a lubricant). The obtained powder mixture was analyzed for bulk density, tapped density, and flow characteristics. Tapped density was determined using an ELECTROLAB tap density tester. The Hausner ratio and compressibility index were calculated using the values of bulk density and tapped density. The flowability of the powder was assessed by passing it through orifices of various diameters ranging from 10mm to 26mm. The mixture was compressed using the tablet compression machine ACCURA mini rotatory tablet press with 9.5mm, round, S/C B tools to form tablets. The resulting tablets were analyzed for weight variation, thickness, hardness, friability, disintegration time, assay, and in-vitro dissolution. Thickness was measured using vernier calipers, and hardness using Pharmatron 6D-Tablet hardness tester. Friability was determined using VANDERKAMP 10809 friabilator counter. Disintegration time was measured in vitro in 900 ml of water at 37 ± 2°C. In-vitro dissolution was measured using the USP monograph method. The amount of model drugs in the assay and dissolution samples was quantified using HPLC.

Results: In the pre-formulation study, DSC analysis of the drug, 1:1 physical mixture of drug and excipients, and the excipient mixture showed no significant changes in the melting point of model drugs as depicted in Figure 1 using caffeine as an example. The powder mixture underwent precompression testing, and the parameters listed in Table 1 were evaluated. The powder exhibits poor flowability based on the values of Carr’s index and Hausner ratio. Upon the post-compression evaluation, all the prepared tablets demonstrate weight variation, thickness, hardness, and average drug content within the acceptable limits defined by the United States Pharmacopoeia [4]. Furthermore, the tablets showed less than 1% friability. The date showed that the tablets have excellent hardness, rapid disintegration time, and achieved over 90% in-vitro drug dissolution within a duration of 15 mins.

Conclusion: Orally disintegrating tablets of drug molecules with varied physicochemical properties are prepared and characterized. In-vitro dissolution shows more than 90% drug release within 15 mins. The characterization results indicate tablets comply with the limits established by the pharmacopoeia to use in human pharmacokinetic studies.

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. Hannan, P. A., et al. "Oral dispersible system: A new approach in drug delivery system." Indian journal of pharmaceutical sciences 78.1 (2016): 2.
3. Hooda, Rakesh, Mohit Tripathi, and Kiran Kapoor. "A review on oral mucosal drug delivery system." The pharma innovation 1.1 (2012).
4. United States Food and Drug Administration. Orally disintegrating tablets. Guidance for industry. Rockville. Maryland: FDA; 2008.

Fig. 1: DSC thermogram of caffeine, a 1:1 physical mixture of caffeine and excipients, and mixture of excipients.

Table 1: Formulation composition of orally disintegrating tablets of Caffeine, Verapamil, Atenolol, Propranolol, and Naproxen

Table 2: Analysis of the powder mixture of model drugs
Table 3: Post-compression parameters of model drugs