DEVELOPMENT OF FLURBIPROFEN SODIUM ORAL DISINTEGRATING TABLETS BY DIRECT COMPRESSION AND SUBLIMATION TECHNIQUE

DEVELOPMENT OF FLURBIPROFEN SODIUM ORAL DISINTEGRATING TABLETS BY DIRECT COMPRESSION AND SUBLIMATION TECHNIQUE

Manoj Prabhakar and K. Rajitha *

Vaagdevi Institute of Pharmaceutical Sciences, Bollikunta, Warangal, Telangana, India.

ABSTRACT: Objective: The present work aimed to prepare flurbiprofen tablets using different concentrations of super disintegrants like croscarmellose sodium, sodium starch glycolate cross povidone sublimating agent thymol. Methods: The tablets were prepared by direct compression and sublimation technique using different concentrations of super disintegrants. The prepared tablets were evaluated for different parameters like hardness, friability, weight variation, thickness, content uniformity, wetting time, disintegration time, and dissolution study. Morphology of pure drug and optimized formulation were revealed by using SEM. Results: All the formulations prepared with the highest concentration of super disintegrant showed the highest drug release. Formulations from F11 to F13 were prepared with the sublimation technique. F11 formulation showed the highest drug release because of its porous nature, which resulted from the sublimation technique. Conclusion: The optimized formulation of the sublimation method (F11) was porous in nature. In-vitro drug release of all formulations prepared with the highest concentration of super disintegrant showed higher drug release than lower concentrations. The formulations prepared by the sublimation technique showed good drug release compared to the direct compression method.

Keywords: Oral route, Sublimation, Thymol, Super disintegrant, SEM

INTRODUCTION: Oral drug delivery is the most widely utilized route of administration among all the routes that have been explored for systemic delivery of drugs via pharmaceutical products of different dosage forms ¹. The oral route is considered as the most natural, uncomplicated, convenient, and safe due to ease of administration, patient acceptability, and cost-effective manufacturing process ². Orally disintegrating tablets immediately release the active drug when placed on the tongue, by rapid disintegration, followed by dissolution of the drug ³.

The objective of this study was to formulate and evaluate tablets of flurbiprofen sodium by direct compression and sublimation technique. A propionic acid derivative, Flurbiprofen was a nonsteroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic activity. Oral formulations of Flurbiprofen may be used for the symptomatic treatment of rheumatoid arthritis, osteoarthritis and ankylosing spondylitis ⁴. In this study, various formulation trails of flurbiprofen sodium tablets were prepared using three super disintegrants: croscarmellose sodium, sodium starch glycolate, crospovidone and sublimating agent thymol.

All the tablets were subjected to drug-polymer interaction studies, weight variation, hardness, friability, disintegrating time, wetting time, drug content uniformity and in-vitro drug release and stability studies ⁵.

Hence, this combined approach was alternative for the preparation of the immediate-release tablets.

MATERIALS AND METHODS:

Materials: Flurbiprofen sodium (JP Fine chemicals, Pune), Microcrystalline cellulose (Degussa India Pvt. Ltd., Mumbai L. R), Croscarmellose (S. D. Fine Chem. Ltd., Mumbai. L. R), Sodium starch glycolate (S. D. Fine Chem. Ltd., Mumbai. L. R), Crospovidone (S. D. Fine Chem. Ltd., Mumbai. L. R), Thymol (S. D. Fine Chem. Ltd., Mumbai. L.R), Talc (Loba Chem. Pvt. Ltd., Mumbai, India), Magnesium Stearate (Degussa India Pvt. Ltd., Mumbai L. R), Aapartame (S. D. Fine Chem. Ltd., Mumbai. L. R), UV-Visible Spectrophotometer (Model UV- 2460, Lab India (UV-3000)), USP Type-II Dissolution Apparatus (Lab India (DS-8000)), Tablet punching machine-12 Stations (Remeik), FT-IR Spectrophotometer, FT-IR 200(Shimadzu Corporation, Japan), Scanning Electron Microscopy (JEOL JSM-6300) (Shimadzu Corporation, Japan).

Methods:

Preparation of Flurbiprofen Sodium Oral Disintegrating Tablets by Direct Compression Method: Oral dispersible tablets of Flurbiprofen sodium were prepared by using the direct compression method according to the formula given in Table 1. Flurbiprofen sodium, crosscarmellose sodium /sodium starch glycolate /crospovidone, aspartame and microcrystalline cellulose are passed through sieve no 40 and blended it for 2 min. To this add magnesium stearate and talc which was previously passed through sieve no 60 and blend for 1 min ⁶. Then compress the blend by using 9 mm punch ⁷. The prepared tablets are evaluated for hardness, friability, weight variation, thickness, content uniformity, disintegration time and dissolution study ⁸.

TABLE 1: FORMULATION DESIGN OF FLURBIPROFEN SODIUM DIRECTLY COMPRESSED TABLETS

Preparation of Flurbiprofen Sodium Porous Tablets by Sublimation Technique: Sublimed tablets of Flurbiprofen sodium tablets were prepared by sublimation technique.

The basic principle involved in the preparation of oral dispersible tablets by sublimation technique was addition of inert solid ingredients (thymol) were added to tablet excipients and the blend was compressed in to tablet ⁹. The composition of formulations was given in Table 2. The drug mixed with other excipients like diluents, thymol, combination of thymol with super disintegrant and aspartame. To this add magnesium stearate and talc which was previously passed through sieve no 60 and blend for 1 min.

Then compress the above blend by using 9 mm punch ¹⁰. After compression tablets were sublimated at 65^οC for 2 h. The prepared tablets are evaluated for hardness, friability, weight variation, thickness, content uniformity, wetting time, disintegration time and dissolution study ¹¹.

TABLE 2: FORMULATION DESIGN OF FLURBIPROFEN SODIUM SUBLIMED TABLETS

RESULTS AND DISCUSSIONS: The granu-lation characteristics are the most important interest to formulation scientists and, therefore, most universally measured. These basic measurements of the granulation have been used to develop and monitor the manufacture of many successful pharmaceutical dosage forms ¹². Blend ready for compression containing drug and other excipients are subjected to pre-compression parameters (micrometric properties) to study its flow properties so as to achieve uniformity of tablet weight ¹³. The results of pre-compressional parameters like bulk density, tapped density, compressibility index, and hausner’s ratio are given in Table 3. Bulk density may influence compressibility, tablet porosity, dissolution, and other properties and depends on the particle size, shape, and tendency of particles to adhere together ¹⁴.

The bulk density and tapped density of powder blend of Flurbiprofen sodium was found to be between 0.452±0.015 to 0.484±0.039 and 0.521±0.023 to 0.649±0.019. The values of bulk density and tapped density lies within the acceptable range; from this the % compressibility of the powder can be calculated. Carr’s index was found to be between 11.13 to 27.77. Hausner’s ratio is a simple method to evaluate powder column stability and estimate flow properties. Hausner’s ratio was found to be 1.126 to 1.385. A low range was observed in Hausner’s ratio, which indicates good flowability ¹⁵. The angle of repose of all the formulations was observed within the range of25.39±0.070 to 25.25±0102 to 29.28±0.061. All the formulations showed an angle of repose below 30^o, which indicates a good flow property.

TABLE 3: PRE-COMPRESSIONAL PARAMETERS OF DIRECT COMPRESSION AND SUBLIMED FORMULATIONS

The hardness values are in the range between 2.8±0.09 to 3.2±0.12 kg/cm² for directly compressed tablets and for sublimed tablets, ranging from 2.5±0.06 to 2.8±0.07 kg/cm ².

TABLE 4: POST-COMPRESSIONAL PARAMETERS OF DIRECTLY COMPRESSED AND SUBLIMED FLURBIPROFEN SODIUM TABLETS

Tablet means thickness (n=3) was almost uniform in all the formulations, and values are ranged from 3.01±0.01mm to 3.08±0.002mm for directly compressed tablets, and for sublimed tablets ranged from 3.04±0.03mm to 3.04±0.03mm.

The standard deviation values indicated that all the formulations were within the range and showed uniform thickness.

TABLE 5: CONTENT UNIFORMITY OF VARIOUS FORMULATIONS OF FLURBIPROFEN SODIUM

Each values represents the mean ± SD n=6

All the prepared tablets comply with the Indian Pharmacopoeia standard for weight variation and friability Table 4. The drug content was found to be in the range of 95.002±0.945% to 101.05±0.284% for the tablets prepared both by sublimation and direct compression method Table 5. It indicates good content uniformity in all formulations. The wetting time studies of prepared porous tablets were performed in phosphate buffer at the pH of 6.8, and the results are presented as percentage weight change concerning time in hrs shown in Table 6. Different formulations have different wetting times; these are obtained by using various types and concentrations of superdisintegrants and sublimating agents for various formulations ¹⁶. The directly compressed tablets with croscarmellose sodium showed less wetting time than the tablets containing cross povidone and sodium starch glycolate. The formulations prepared with croscarmellose and thymol showed less wetting time than those prepared with only croscarmellose sodium tablets.

TABLE 6: WETTING TIME PROFILES OF BOTH DIRECTLY COMPRESSED AND SUBLIMED TABLETS

Disintegration time of various formulations were determined and values were showed in Table 7 and Fig. 1 and 2, F11 formulation showed less disintegration time compared to all other formulations which was formulated by sublimation technique because of its porosity it disintegrates within seconds compared to the formulations prepared by direct compression method ¹⁷.

TABLE 7: DISINTEGRATION TIME (SEC) PROFILES OF FLURBIPROFEN SODIUM IN VARIOUS FORMULATIONS

FIG. 1: DISINTEGRATION PATTERN OF F11

FIG. 2: DISINTEGRATION PROFILE OF VARIOUS FORMULATIONS

Drug release studies were carried out for both directly compressed and sublimed tablets of Flurbiprofen sodium by using USP type II (paddle) apparatus. 900 mL phosphate buffer pH 6.8 was used as dissolution medium, and the paddle was rotated at 60 rpm at temperature (37^oC ± 0.5^oC). After each sampling interval, sampling was done at regular intervals and replaced by fresh media. The samples are then analyzed spectrophotometrically at λ_max of the drug (i.e 247nm). In the case of the directly compressed Flurbiprofen sodium tablets, the effect of superdisintegrant on the drug release relatively to time was determined. In the case of sublimed tablets of Flurbiprofen sodium, the effect of super disintegrant and sublimating agent on the amount of drug release relatively to time was determined¹⁸. Experimentally the release rate of the formulation without any superdisintegrants (F10) was also studied in phosphate buffer pH 6.8 showed less amount of drug release than the sublimed and directly compressed tablets.   Table 8 and Fig. 3 and 4 summarize the % drug release from the directly compressed Flurbiprofen sodium tablets at various time intervals using sodium starch glycolate, cross caramellose sodium, and crospovidone as super disintegrants.

The % drug release values increased with an increase in the concentration of the sodium starch glycolate, cross caramellose sodium and cross povidone. The rapid increase in dissolution of sodium starch glycolate was may be due to rapid uptake of water by forming a gel layer, while tablets formulated with croscarmellose sodium disintegrated may be due to swelling and wicking action in primary particles and crospovidone containing tablets disintegrated may be due to its high capillary action and less tendency to gel formation ¹⁹.

TABLE 8: IN-VITRO DISSOLUTION PROFILE OF VARIOUS FORMULATIONS OF FLURBIPROFEN SODIUM

FIG. 3: CUMULATIVE DRUG RELEASE OF DIRECTLY COMPRESSED TABLETS                         

FIG. 4: CUMULATIVE DRUG RELEASE OF SUBLIMED TABLETS OF FLURBIPROFEN SODIUM

For the optimized formulation of prepared tablets, stability studies were conducted and showed in Table 9 there was no changes were observed it indicating that the formulation was stable.

TABLE 9: STABILITY STUDIES OF F11 FORMULATION

Scanning Electron Microscopy: The scanning electron micrographs of pure Flurbiprofen sodium, and optimized formulation tablet are shown in the Fig. 5A and 5B, respectively. Pure Flurbiprofen sodium appears as blunt crystals, with a smooth surface, shown in Fig. 5A. The optimized formulation of the sublimation method (F11) showed the formation of porous nature, which is responsible for rapid disintegration.

FIG. 5: SEM PICTURES (5A) PURE FLURBIPROFEN SODIUM, F11(5B) FORMULATION

CONCLUSION: The present work of this study was to formulate and evaluate porous tablets of flurbiprofen sodium by sublimation technique.

In this study, various formulation trails of flurbiprofen sodium tablets were prepared using three super disintegrants: crosscarmellose sodium, sodium starch glycolate, crospovidone, and sublimating agent thymol. All the tablets were subjected to drug-polymer interaction studies, weight variation, hardness, friability, disintegrating time, wetting time, drug content uniformity and in-vitro drug release and stability studies. Hence, this combined approach was an alternative for preparing the immediate-release tablets.

ACKNOWLEDGEMENT: The authors would like to thank St. Peters College of Pharmacy for providing all the requirements used in the dissertation work.

CONFLICTS OF INTEREST: No conflict of interest.

REFERENCES:

1. Vishali T and Damodharan N: Orodispersible Tablets- A Review. Research Journal of Pharmacy and Technology 2020; 13(5): 1-9.
2. Rahane R, Punit R and Rachh A: A review on fast dissolving tablet. Journal of Drug Delivery & Therapeutics 2018; 8(5): 50-55.
3. Lars Edvinsson R: Oral disintegrating tablet for migrane. The Lancet Publication 2019; 394(10200): 711-712.
4. Shaimaa N. Alhammid M and Haider H: Formulation and Evaluation of Flurbiprofen Oral Film. Iraqi Journal of Pharmaceutical Sciences 2014; 23(1): 53-59.
5. Salatin MS and Nasiri EJ: Preparation and optimization of fast disintegrating tablets of isosorbidedinitrate using lyophilization method for oral drug delivery. Therapeutic Delivery 2020; 12(7): 7-12.
6. Gamal M, Mahrous M, Gabr Kassem M, Abbas Ibrahim and Sayed Hassan: Formulation and evaluation of orally disintegrating clopidogrel tablets. Brazilian Journal of Pharmaceutical Sciences 2016; 52(2): 309-317.
7. Hannan PA, Khan JA, Khan A and Safiullah A: Oral dispersible system-a new approach in drug delivery system. Indian J of Pharma Sciences 2016; 78(1): 2–7.
8. Sujan D, Bipindra P, Sabina N, Yamuna G and Rashmi S: Formulation and Evaluation of Orally Disintegrating Tablet of Metoclopramide Hydrochloride. World Journal of Current Medical and Pharmaceutical Research 2020; 2(6): 322–329.
9. Maimoona C: Recent formulation advances and therapeutic usefulness of orally disintegrating tablets. Pharmacy Basel 2020; 8(4): 186.
10. Runhan, Yilongyang, Xiaoshanli and Defangouyang: Predicting oral disintegrating tablet formulations by neural network techniques. Asian Journal of Pharmaceutical Sciences 2018; 13(4): 336-342.
11. Rajeswari RK, Brungi V, Bennuru S and Cheeli SRM: Gupta Vankadari: Studies on the development of Orally Disintegrating Tablets of Irbesartan. Asian Journal of Pharmaceutical Research 2020; 10(1): 1.
12. Tansel C and EmineDilek O: Orally disintegrating tablets and orally disintegrating mini tablets – novel dosage forms for pediatric use. Pharmaceutical Development and Technology 2019; 24(7): 902-914.
13. Shahinaze A, Fouad D, Fady A, Malaak L, Nabarawi E and Khalid Abu Z: Development of orally disintegrating tablets containing solid dispersion of a poorly soluble drug for enhanced dissolution. In-vitro optimization/in-vivo Plos One 2020; 15(12): 1-17.
14. Raghavendra Kumar G, Prasada Rao M, Chaikam G, Divya K, Alekhya D and Jyoshna E: Formulation development and in vitro evaluation of oral disintegrating tablets for newer anticonvulsant agent. Journal of Analytical and Pharmaceutical Reasearch 2019; 8(2): 85‒89.
15. Swarnalatha N, Vidyavathi M and Kiran Kumar A: formulation, in-vitro and in-vivo evaluation of taste masked oral disintegrating tablets of famotidine. International Journal of Pharmaceutical Research 2021; 14(1): 85-91.
16. Teaima MH, Abdel-Haleem KM, Osama R, Nabarawi MA and Elnahas OS: A promising single oral disintegrating tablet for co-delivery of pitavastatin calcium and lornoxicam using co-processed excipients: formulation, characterization and pharmacokinetic study drug design. Development and Therapy 2021; 15(1): 4229-4242.
17. Avinash D, Madhu G, Ramana M, Pallavi V and Rama Rao N: Mouth dissolving tablets of favipiravir using superdisintegrants: preparation, optimization and in-vitro International Journal of Pharmaceutical Research 2021; l33(6): 28-39.
18. Durgaramani S, Muhammad Hadi S, Osama M, Shamama J and Aamena J: Formulation and in-vitro evaluation of orodispersible tablets of fexofenadine hydrochloride. Tropical Journal of Pharmaceutical Research 2020; 19(5): 919-925.
19. Pabari RM and Ramtoola Z: Effect of a disintegration mechanism on wetting, water absorption and disintegration time of orodispersible tablets. Journal of Young Pharmacists 2020; 4(3): 157-163.
    

    ---

    How to cite this article:

    Prabhakar MM and Rajitha K: Development of flurbiprofen sodium oral disintegrating tablets by direct compression and sublimination technique. Int J Pharm Sci & Res 2022; 13(7): 2703-09. doi: 10.13040/IJPSR.0975-8232.13(7).2703-09.

    ---

    All © 2022 are reserved by International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.