Trigonella foenum-Plantago Ovata Seeds Mucilage as a Superdisintegrants for the Development of Bisoprolol Fumarate Loaded Quick Dissolving Tablet (QDT)

 

Raghavendra Rao N G¹*, Priyanka Gupta², Sheela M A³

¹Department of Pharmaceutics, KIET School of Pharmacy, KIET Group of Institutions, NCR-Delhi,

Ghaziabad-201206, Uttar Pradesh, India.

²Department of Pharmacy, GRD (PG) IMT, 214, Rajpur, Dehradun-248009 Uttarakhand, India.

³Rajkumar Goel Institute of Technology(Pharmacy), Rajkumar Goel Group of Institutions, Delhi-Meerut Road, Ghaziabad, UP, India- 201003.

 

ABSTRACT:

_{Objective: The aim of this present research work, the aim was to develop drug-loaded} Bisoprolol fumarate _{quick-dissolving tablets} by direct compression method by using Trigonella Foenum - Plantago ovata seeds mucilage.  Comparative studies between synthetic and natural superdisintegrants. Bisoprolol Fumarate is an antihypertensive drug incorporated in handling hypertension, and as a prophylaxis treatment of angina pectoris, heart failure. _Methods: Bisoprolol fumarate-loaded tablets _{were developed, estimated for different pre and post-compressional parameters, FTIR study, and short-term stability studies. Results and Discussions: The FTIR spectral analysis results indicate no interaction between the drug and formulation additives.} p_{re and post-compressional parameters were within the authorised Pharmacopeial limits, and the results were satisfactory. The disintegration time and dissolution investigations of formulations F12 and F15 were determined to be the most promising, with disintegration times of 22 and 24 secs, respectively. FormulationsF12 and F15 containing} Trigonella Foenum and plantago ovata mucilage’s _{showed highest drug release above 99% within 20 and 25 min respectively.} Trigonella Foenum mucilage and Plantago ovata was identified to be the better superdisintegrant compare to synthetic superdisintegrants. Stability studies to optimize the formulations were carried out for about 90 days. During the studies, no considerable changes were noticed in the compressed tablets for in-vitro disintegration time, hardness, friability and uniform distribution of drug content etc. _{Conclusion: Based on} disintegration time the developed formulations F3, F12 and F15 were found to be mostly constitutive, with disintegration times of 30, 22, and 24 secs. _{The result outcome can be interpreted that the formulations loaded with Bisoprolol} fumarate have shown _{enhanced dissolution rates that might have been the cause of improved bioavailability, subsequently an effective therapy by coupling with} Trigonella foenum and Plantago ovata mucilage. These mucilages were plant-derived, non-toxic, bio-compatible, bio-degradable, and least side effects.

 

 

 

INTRODUCTION: 

Oral administration of medicines is typically the most favored route for medicines on other routes since they are easy to use, good conformity to patients, safety, cost-effectiveness, less need for sterilization, and  flexibility in dosage form formulation. In spite of all these advantages, oral drugs must have to go through the process of dissolution in the gastrointestinal tract before they appear in the bloodstream through biological membranes.

 

Tablets are the first choice as solid dosage forms for oral dosing for immediate consumption, either chewed or dispersed in water beforehand. Sublingual pills are chewed and dissolved in the mouth and get dissolved with saliva. Patients who are advanced in age often find difficulty in swallowing prescribed conventional tablets and capsules^1-3. Tablet swallowing is a problem with paediatrics, psychiatric patients, and travellers who might not have easy access to water Quick dissolving tablets in the mouth, also known as orodispersible tablets, solve all of the concerns described above, making them an alternative acceptable form of oral medication. By incorporation of superdisintegrants in the formulations is the better choice to develop/design orodispersible tablets^4-11.

 

Fast dissolving dosage form disintegrates faster with saliva. They dissolve when placed on the tongue, it releases the medication instantly. The fast dissolving tablets are helpful to cater to the needs of patients^12,13 including paediatric, geriatric, bedridden, physically challenged, or intellectually handicapped individuals who may have trouble eating traditional foods oral solid medication^14,15. Most of the pharmaceutical oral drugs are manufactured for direct ingestion, chewing or prior reconstitution in water. Very few drugs are suitably designed to become engulfed in the mouth (buccal or sublingual tablet). However, to bridge the gap with the oral conventional dosage forms, tablets with swift dissolution capacity have been developed which the amalgamation of required hardness, content uniformity, stability and other parameters. To administer these tablets neither water nor swallowing is required. Thus they are suitable for all above said groups¹⁶. 

 

Novel drug delivery systems adopt the new advancements to improve patient compliance by reformulating the matching traditional dose forms to improve the safety and efficacy of the medication compounds quickly dissolving tablets are one such endeavour QDT^{17, 18}.

 

Bisoprolol fumarate is a specific beta adrenoceptor antagonist that inhibits catecholamine activation of 1-adrenergic sites in the heart and vascular smooth muscle, resulting in a significant reduction in pulse rate, cardiac output, and plasma renin levels¹⁹. Hence it is used to treat angina pectoris, arrhythmias and hypertension²⁰.

 

The half-life of the drug is 10 hrs and bioavailability is more than 80%. The drug has relatively high bioavailability and half-life. _{The main objective of the present study is to place a fruitful attempt that has been made to design drug-loaded} Bisoprolol fumarate quick-dissolving _{tablets prepared by using} both natural and synthetic superdisintegrants to explore the upgraded benefits of biodegradability, hydrophilicity, cytocompatibility, minimum toxicity, and biocompatibility of the Trigonella Foenum mucilage and Plantago ovata Forssk.

MATERIALS AND METHOD:

The Active Pharmaceutical Ingredient Bisoprolol fumarate was procured from Medicamen organics limited, Haridwar, India. Other excipients Crosscarmellose sodium, Crospovidone, and Sodium starch Glycolate were procured from HiMedia Laboratories Ltd, Mumbai. Microcrystalline cellulose, Aspartame, and Mannitol were obtained by Accord Labs, Secunderabad. Magnesium stearate and talc were procured by Finar chemicals Ltd, Mumbai. Pure Trigonella Foenum and Plantago ovata were purchased at the local market of Dehradun, Uttarakhand.

 

Isolation of Plantago ovate Mucilage:

Plantago ovate seeds were steeped in distilled water for 48 hours before being cooked for the next few minutes. On slow heating to ensure all the mucilage completely gets released into water^21-23. Allowed to cool down, then squeezed through a clean muslin cloth to separate the marc. The collected marc was mixed with an equivalent volume of acetone mixed well so as to precipitate the mucilage. Mucilage was separated out, and subjected to drying in an oven at a temperature of less than 60°C. The obtained mucilage was powdered, sieved through #80 meshes, and placed in a desiccator for further use.

 

Isolation of Fenugreek Mucilage:

100 gm Fenugreek seeds were weighed steeped in 600 ml distilled water for 24hrs in a 1000 ml beaker. Then fenugreek was ground in a clean grinder jar, and was warmed for 30 min. Cooled down and was passed through a clean muslin bag then squeezed to remove all possible mucilage. For the mucilage precipitation, acetone (same quantity) was applied to the collected filtrate and kept at low temperature (inside a refrigerator) for 24 hours. It was dried completely in an incubator at 40-45°C, finally filtered by using #80 mesh, and stored dry powder carefully from the outer atmosphere.

 

Swelling capacity:

Swelling index is the quantity in ml that 1 gm of medication or any adherent mucilage takes up after 4 hours of swelling in an aqueous liquid. The swelling index for plantago ovata, fenugreek, crosscarmellose sodium, crospovidone, and sodium starch glycolate was determined using the BP technique. The swelling index was derived using the average results from all three measurements.

 

Table 1: Swelling capacity of superdisintegrant.

Table 2: Formulation Composition of Drug loaded Bisoprolol Fumarate QDT

BF: Bisoprolol fumarate, FSM: Fenugreek seed mucilage, POM: Plantago ovata mucilage, MS: Magnesium stearate.

 

Preparation of Quick dissolving tablets (QDT) of Bisoprolol Fumarate:

Bisoprolol Fumarate Quick dissolving tablets (QDT) were prepared using direct compression method as shown in table-2. All the excipients were accurately weighed and passed through a 60 mesh filter individually, as required by the formula. The drug (API) and microcrystalline cellulose were added in small amounts in geometric sequence each time, and then blended to make a uniform mixture. Tablets were compressed using a multi-station tablet punching machine with an 8mm flat round punch. Each formulation was made into fifty tablets.

 

METHODOLOGY:

API and additives compatibility data:

FTIR studies:

An outstanding formulation of any drug delivery formulation depends upon the proper selection of all the additives employed in the formulations. Constituents are used to make the drug easier to administer, release consistently, and increase bioavailability. As a result, it is critical to look into the excipients' compatibility with the drug. The IR spectroscopy approach was utilized to study and forecast any physicochemical interactions and incompatibilities between the drug and excipients. All of the combinations were subjected to FTIR studies, with spectral data collected in the wavelength range of 4000 to 400 cm^-1. The technique involved spreading a sample, drug alone, or a combination of drug and polymers in KBr and compressing into discs under 7 tonnes of pressure for 5 mins in KBr pellets. The spectral data was acquired when the pellet was put in the light path.

 

Evaluation of pre-compression parameters²⁴:

The prepared powder blends of formulation batches were evaluated for pre-compression parameters in order to study their bulk density, tapped density, Carr’s index and flow properties. We calculated the compressibility index, Carr's index, and Hausner's ratio. The angle of repose was used to determine the flow parameters of the powders.

 

Post-compression investigations of QDT^25-36:

Hardness test:

The strength/hardness of the compressed tablets were tested. The hardness of the tablets was measured with a Pfizer Hardness tester and represented in Kg/cm². Three tablets were chosen at random from each formula, and the mean and standard deviation were calculated.

 

Friability test:

The capacity of compressed tablets to withstand mechanical shocks such as wear and tear, handling, packaging, and transportation was investigated. Twenty tablets were initially weighed (W_initial) and transferred into a friabilator. The friabilator was operated at 25 rpm for 4 min or run up to 100 revolutions. The tablets were weighed again (W_final).

 

The percentage friability was estimated using the following formula.

F =   

A percentage of friability of less than 1% is regarded to be acceptable.

 

Weight variation test:

To assess for weight variance, compressed tablets were randomly picked from each formulation and individually weighed. According to the United States Pharmacopoeia, slight weight variations within the acceptable limits are agreeable.

 

The weight of the tablet was greater than 130 mg but less than 324 mg in all the formulations. The maximum weight variation difference observed was: 7.5% (within the Pharmacopoeia limit).

 

Uniformity of thickness:

Individual tablets were measured for crown thickness with the help of a micrometer for an accurate measurement. Other techniques selected to check Production management include putting 5 or 10 tablets in a holding tray and using a sliding caliper scale to assess overall crown thickness.

Drug content uniformity:

Five tablets were weighed and pulverized separately. The content of the medicine was evaluated by measuring absorbance at max 222 nm using a spectrophotometer after weighing, mixing, and extracting 20 mg of Bisoprolol fumarate powder in 100 ml water.

 

Wetting time:

A tablet was placed on a piece of tissue paper folded twice in a tiny petri dish containing 10 ml of water (i.d = 6.5 cm), and the time for full soaking was measured. Each batch was subjected to three trials, with standard deviation taken into account.

 

In-vitro disintegration time:

Disintegration is to release the drug, a tablet is broken down into tiny particles. The tablet breakdown time of each tablet was calculated using a disintegration test instrument in accordance with Indian Pharmacopeia norms. A single tablet should be placed in basket of disintegrating unit. The apparatus consists of minimum 6 tubes of baskets. Following the addition of a disc to each tube, the equipment was run with distilled water at 37°±2°C. The assembly should be raised and immersed into the water between 30 cycles per min. The time taken was noted accurately for total tablet breakdown with no perceptible substance left in the baskets.

 

In-vitro dissolution studies:

The in-vitro dissolution of the prepared tablet was accomplished by using the Dissolution Apparatus of the USP-II. The tablets were kept in the dissolution apparatus. 900 ml of distilled water was taken as dissolution media and the apparatus was set at rpm 50 and temperature 37⁰ C. 5ml sample was drawn at the interval of 5 min for the first 30 min and later on at 15 min of interval for 1 hr. The aliquots were collected and replaced by distilled water every time in an individual dissolution vessel. Absorbances of the drawn samples were measured using UV spectrophotometer at λmax 222 nm and percentage drug release profile was identified.

 

Optimized factorial batch accelerated stability study³⁷:

·         As part of the drug discovery, the stability test of drug products begins and ends until the molecule or commercial product has been removed.

·         The ICH Guidance Q1C formulations were most satisfactory in stability testing.

·         The stability of any drug attributes to its potential to combat deterioration. The minimal acceptability potency level is widely accepted to be 90% of the declared strength. Deterioration of a drug may be of several reasons right from physical changes or chemical changes and even microbiological attacks etc.

·         Stability studies for three months, the tablets were stored in stability chambers at temperatures of 25°C ± 2°C/60 % RH 5% (long-term) and RH 40°C± 2°C/75 % RH 5% RH (accelerated) (Thermo Lab, Mumbai).

 

RESULTS AND DISCUSSION:

Drug excipients compatibility studies FTIR:

Possible drug and polymer interactions and compatibility profiles were investigated by FTIR. Pure Bisoprolol Fumarate was shown characteristic stretching absorption bands of-OH at 3506, of –NH group at 3044, of aromatic (CH=CH), aliphatic alkane stretching (C–H and CH₂) vibration at 2974, 2866, 2825 cm⁻¹. The bending vibration of asymmetric CH₃ is observed at 1469 cm⁻¹ and 1421 cm⁻¹. The absorption bands for C-O appeared at 1238 cm⁻¹ and 1093 cm⁻¹ respectively.

 

 

Fig 1: IR spectrum of Bisoprolol fumarate, IR spectrum of Drug + CP, Drug + Fenugreek seed mucilage, Drug + SSG, Drug + Plantago ovata mucilage and Drug + CCS.

 

The IR spectrum of Bisoprolol Fumarate and excipients clearly indicates that the peaks did not change revealing that there was no interference between the drug and excipients, the prominent peaks of Bisoprolol Fumarate reactive functional groups absorption bands of –OH and -NH group are present in the spectra of different formulations. Pure drug and excipients absorption bands values indicating that there was no chemical and physical change in the functional groups present in Bisoprolol Fumarate. (Shown in Fig 1).

 

Evaluation of Pre-Compressional parameters:

Table 3 depicts the powder blend properties of Bisoprolol fumarate-loaded QDT. The powder blends were evaluated by following pre-compressional parameters. The observed pre-compressional parameters were within the IP limits, and the free flow property was satisfactory as per table-3.

 

The findings of the post-compressional investigation were displayed in (Table 4). Hardness testing showed high mechanical strength in all formulations. The tablets were found to have a hardness of 3.1-4.1 kg/cm². The range of friability is 0.22 to 0.54 %, which is well within the allowed limit. (<1%) attribute that tablet had good strength to withstand mechanical wear and tear. All prepared tablets passed the weight variation test; the average percentage of weight variation was 7.5%. In all developed formulations, weight variation was found to be between 197.1 and 201.5 mg. The drug content was determined to be high (100%) and consistent across all formulations. The drug concentration was determined to be between 97.48 and 100.10 percent (acceptable limit). The wetting time was an essential criterion for determining disintegrants' ability to swell with a small amount of water. The swelling index ranged from 21 to 72 sec (Table 4). All the formulations showed rapid disintegration within a few minutes. The disintegration periods in vitro were found to be between 22 and 177 sec.

 

Table 3: Pre-compressional parameters of Bisoprolol fumarateloaded Quick Dissolving Tablet Formulation.

*The values represent mean± S.D; n=3, FC = Formulation Code.

However, the incorporation of superdisintegrants significantly improved the disintegration time (P<0.05). Gleaned from disintegration time of prepared formulations F3, F12 and F15 were found to be the most promising formulations and exhibit better disintegration time of 30, 22, and 24secs respectively. These results suggest that the use of superdisintegrants can reduce disintegration times.

 

Table No 4: Post-Compressional parameters of drug loaded Bisoprolol fumarateFast Dissolving Tablets.

FC=Formulation code, **All the values expressed as mean ±SD, n=10, *All the values expressed as mean ±SD, n=3. ***All the values expressed as mean ±SD, n=6.

Plantago ovata and Fenugreek seed mucilage were utilised as superdisintegrating agents in this investigation. This is mostly due to the quick absorption of water from the medium, which creates swelling and a burst effect.

 

In-vitro drug release study:

The dissolution rate of Bisoprolol fumarate Quick Dissolving Tablets was tested using a USP Type-II dissolution device at 75 RPM and 900 ml of water as the dissolution medium at 37±0.5ºC, aliquots were of collected at a specific interval of time. After filtration, their absorbance was identified. The concentration of the medication was measured from the standard calibration curve using a UV spectrophotometer (Shimadzu, Japan) set to 222 nm.

 

A steady increase in the rate of dissolution was observed with the increase in the concentration of superdisintegrants. The decrease in disintegration time was evident that Superdisintegrants are used in a specific tablet formulation in larger amounts as per the need.

 

The dissolution patterns derived were shown in figures 3 and 4. The dissolution results of formulations (F1 – F15) were shown the optimum release of drug 90 % within 60 min. The formulations F12 and F15 show 99% of drug release within 20 and 25 mins respectively. Fenugreek seed mucilage containing formulation and plantago ovata mucilage containing formulations represents the Due to the obvious swelling properties of Fenugreek seed and plantago ovata mucilages, the medication is released quickly. The F3 formulation, on the other hand, displays 99% drug release in 30 mins. Tablets containing crospovidone showed fast capillary activity and considerable hydration, with a small propensity to gel. F3 identified as a quick-dissolving tablet containing 15 mg of crospovidone as superdisintegrating agent. F12 and F15 emerged as quick-dissolving tablets containing 15 mg of Fenugreek seed mucilage as super disintegrating agent.

 

 

Fig 3: The drug release from Bisoprolol fumarate loaded Quick Dissolving tablet formulations F1- F9.

 

Fig 4: The drug release from Bisoprolol fumarate loaded Quick Dissolving tablet formulations F10- F15.

 

Table 5: Stability study results for 3 months of promised formulations 25⁰C/60 %  & 40⁰ C/75 % RH.

 

Stability studies:

Table 5 shows various characteristics of the stability study. The optimized formulations were selected for the studies. These were carried out in accordance with the ICH Q1C criteria. For three months, the improved formulations F3, F12, and F15 were held at increased temperatures of 25°C/65 % RH and 40°C/75 % RH. The optimized formulations were tested for hardness, friability, drug content, and disintegration time throughout the course of 90 days of stability studies was found there were not any significant changes of all three formulations (F3, F12, and F15). Thus, the results were successful compared to the remaining batch formulations, with a stable and effective rapid-release tablet with natural super disintegrants.

 

This research work was an effort made to prepare Bisoprolol Fumarate loaded Quick Dissolving tablet formulations were prepared by direct compression method using synthetic and natural superdisintegrants. Overall results indicate that formulation F3 shows 99% of drug release within 30 min. With a high capillary activity and more hydration, crospovidone containing tablets have shown immediate results and slight gelling property. The formulations F12 and F15 shows 99% of drug release within 20 and 25 mins respectively. Fenugreek seed mucilage containing formulation and plantago ovata mucilage containing formulations shown rapid release. That is owing to the fact that mucilage of Fenugreek seeds has a higher swelling property and plantago ovata mucilage’s. The present research outcome finally revealed that the natural superdisintegrant Fenugreek seed mucilage and plantago ovata mucilage proved the very best quick disintegrating ingredient in manufacture of quick-dissolving tablets than the most extensively used synthetic superdisintegrants. Natural superdisintegrants, have several benefits over synthetic superdisintegrants, including multifunctionality, natural abundance, biodegradability, hydrophilicity, cytocompatibility, minimum toxicity, and biocompatibility.

 

CONFLICT OF INTEREST:

The author has no conflict of interest.

 

REFERENCES:

1.   Rajitha K, Shravan YK, Adukondalu D, Ramesh G, Rao YM. Formulation and evaluation of orally disintegrating tablets of buspirone. Int J Pharm Sci Nanotechnol 2009; 1:327-34. doi.org/10.37285/ijpsn.2008.1.4.3.

2.   Chang RK X. Guo BA. Burnside RA. Cough. Fast dissolving tablets. Pharm Tech 2000; 24:52-58. E-LIBRARY ID: 6095733.

3.   Yeola BS, Pisal SS, Paradkar AR, Mahadik KR. New drug delivery systems. Indian Drugs 2000; 37(7):312-318.

4.   Watanabe Y, Koizumi K, Zama Y, Kiriyama M, Matsumoto Y, Matsumoto M. New compressed tablet rapidly disintegrating in saliva in the mouth using crystalline cellulose and a disintegrant. Biol Pharm Bull 1995; 18(9):1308-10. DOI: 10.1248/bpb.18.1308.

5.   Bi Y, Sunada H, Yonezawa Y, Danjo K, Otsuka A, Iida K. Preparation and evaluation of a compressed tablet rapidly disintegrating in the oral cavity. Chem Pharm Bull (Tokyo) 1996;44(11):2121-7. DOI: 10.1248/cpb.44.2121.

6.   Ishikawa T, Watanabe Y, Utoguchi N, Matsumoto M. Preparation and evaluation of tablets rapidly disintegrating in saliva containing bitter taste masked granules by the compression method. Chem Pharm Bull (Tokyo) 1999; 47:1451-4. DOI: 10.1248/cpb.47.1451.

7.   Ishikawa T, Koizumi N, Mukai B, Utoguchi N, Fujii M, Matsumoto M, et al. Pharmacokinetics of acetaminophen from rapidly disintegrating compressed tablet prepared using microcrystalline cellulose (PH-M-06) and spherical sugar granules. Chem Pharm Bull (Tokyo) 2001; 49:230-2. DOI: 10.1248/cpb.49.230.

8.   Grassano A, Marchiorri M, Ditoro M, Castegin F. Fast dissolving compositions having analgesic activity. US patent. 2001; 6:197, 336. I E990557A1.

9.   Gills PM, Deconde VF. Fast dissolving galanthamine hydrobromide tablet. US patent. 2000; 6:099.863. US6099863A.

10. Makooi Morehead WT, Buehler JD, Landmann BR. Formulation of fast dissolving efavirenz capsules or tablets using super disintegrants, US patent. 2001; 6:238, 695. US6238695B1.

11. Grassano A, Marchiorri M, Ditoro M, Castegin F. Fast dissolving compositions having analgesic activity. US Patent. 2001; 6:197, 336. EP 1 100 470 B1.

12. Chue P, Welch R, Binder C. Acceptability and disintegration rates of orally disintegrating risperidone tablet in patients with schizophrenia or schizoaffective disorder. Can. Jr. Psychiatry. 2004; 49:701-3. doi: 10.1177/070674370404901009.

13. Shu T, Suzuki H, Hirohonda, K. Studies of rapidly disintegrating tablets in oral cavity using co-ground mixture of mannitol with crospovidone. Chem. Pharm. Bull. (Tokyo). 2002; 50:193-8. DOI: 10.1248/cpb.50.193.

14. Seager H, Drug delivery products and the zydis fast dissolving dosage form. Jr. Pharm. Pharmacol. 1998; 50:375-382. DOI: 10.1111/j.2042-7158.1998.tb06876.x.

15. Fini Adamo, Valentina Bergamanate, Gian Carlo Ceschel, Celestino Ronchi, Carlos Alberto Fonseca de Moraces, Fast dispersible/slow releasing ibuprofen tablets, Eur.Jr. Pharm and biopharm. 2007: 335-341. DOI: 10.1016/j.ejpb.2007.11.011.

16. Seong Hoon Jeong, Yuuki Takaishi, Yourong fu and Kinam Park. Material properties for making fast dissolving tablet by a compression method.  J. Mater. Chem. 2008; 18:3527-3535. doi.org/10.1039/B800209F.

17. Dobetti L. Fast melting tablets: Developments and Technologies. Pharma Tech 2001; Suppl:44-50. Corpus ID: 13788707.

18. Kuchekar BS, Arumugam V. Fast dissolving tablets. Indian J Pharm Educ Res 2001; 35:150-2.

19. Sean C, and Sweetman A, "Martindale the Complete Drug Refrences" 35th edited by Phamaceutical Press, 2006. p875.

20. Prichard BN. Bisoprolol: a new betaadrenoceptor blocking drug. Eur. Heart J. Suppl 1M., 1987. 121(9). DOI: 10.1093/eurheartj/8.suppl_m.121.

21. Washi SP, Sharma VD and Sinha P. (1985). Plantago ovata: genetic diversity, cultivation, utilization and chemistry. Indian J Nat Prod.1:3-6. D OI: https://doi.org/10.1079/PGR200582.

22. Bavega SK, Rao KV and Arora J. (1989). Examination of natural gums and mucilages as sustaining materials in tablet dosage forms. Part-II. Indian J Pharm Sci.51:115-118.

23. Basawaraj S. Patil, Raghavendra Rao NG. Formulation and evaluation of fast dissolving tablets of Candesartan Cilexetil using natural and synthetic Superdisintegrants. Journal of Applied Pharmacy. JAP: 03(03): 250-261 (2011). doi:10.21065/19204159.3.250.

24. Vikash Jakhmola, Raghavendra Rao NG, Raja Ram Mohan Rai. Formulation and Evaluation of Mouth dissolving tablet of Zafirlukast using directly compressible excipients: a Review. International Journal of Research and Analytical Reviews (IJRAR): May 2020, 7(2):189-193. IJRAR19L1410.

25. Chandran CS, Shijith KV, Vipin, Augusthy AR. Chitosan Based Mucoadhesive Buccal Patches Containing Bisoprolol Fumarate. Int J Adv Pharm Bio Chem. 2013; 2(3): 465-469. ID: 53605331

26. Basawaraj S.Patil, Raghavendra Rao NG, Dayakar Rao K. Formulation and Evaluation of Fast Dissolving Tablets of Granisetron Hydrochloride. International Journal of Applied Biology and Pharmaceutical Technology. IJABPT: Vol: 2: Issue-2: Apr-June 2011, 22-28.

27. Basawaraj S. Patil, Raghavendra Rao NG. Enhanced Dissolution and Bioavailability of Granisetron Hydrochloride By Direct Compression Technique.International Journal of Medical and Pharmaceutical Sciences. IJMPS:2011: Vol 1: issue 4; 1-9.

28. Priyanka Joshi, Manju, Mohd Vaseem Fateh, Raghavendra Rao NG. Review on Mouth Dissolving Tablet. Asian Journal of Pharmaceutical Research. AJPR: 9(1): January- March, 2019: 42-54. DOI: 10.5958/2231-5691.2019.00008.X .

29. Prathibha Suvarna, Ravi Kumar, Yamunappa, Pooja Shetty, Narayana Swamy VB. Development and In Vitro Evaluation of Fast Dissolving Tablets of Tapentadol. Asian Journal of Pharmaceutical Research. Asian J. Pharm. Res. 6(1): January -March, 2016; Page 11-21. DOI: 10.5958/2231-5691.2016.00003.4.

30. Avinash Bhagwat, Suhas M Kakade, Chirag V Naval, Mukesh Tilker, Ravindra M Walture, Sagar A Adichwal, and Atul P Chaudhari. Formulation and Evaluation of Mouth Dissolving Tablets of Domperidone. Research Journal of Pharmacy and Technology. Research J. Pharm. and Tech.3 (3): July-Sept. 2010; Page 821-824.

31. Mahaveer Singh, Gautam Singhvi, SG Kaskhedikar, Love soni. Development of Fast Dispersible Tablets of Carvedilol: Effect of Functionality of Superdisintegrants. Research Journal of Pharmacy and Technology. Research J. Pharm. and Tech.3 (3): July-Sept. 2010; Page 942-944

32. Bhalerao AV, Deshkar SS, Shirolkar SV, Gharge VG, Deshpande AD. Development and Evaluation of Clonazepam Fast Disintigrating Tablets Using Superdisintigrates and Solid Dispersion Technique. Research Journal of Pharmacy and Technology. Research J. Pharm. and Tech.2(2): April.-June.2009; Page 375-377.

33. Jagdale SC, Chabukswar AR, Kuchekar BS, Padalkar AN, Kale AU. Comparative Evaluation of Superdisintegrants with Formulation Development of Orodispersible Tablets of Mosapride Citrate Dihydrate. Research J. Pharm. and Tech. 2(1): Jan.-Mar. 2009; Page 91-96.

34. Uday S Rangole, PS Kawtikwar, DM Sakarkar. Formulation and In-vitro Evaluation of Rapidly Disintegrating Tablets Using Hydrochlorothiazide as a Model Drug. Research J. Pharm. and Tech. 1(4): Oct.-Dec. 2008; Page 349-352.

35. Shailesh Sharma, Sudhir Bharadwaj, Gupta GD. Fast dissolving tablets of Promethazine theoclate by using natural superdisintegrants. Research J. Pharm. and Tech. 1(3): July-Sept. 2008; Page 218-224.

36. Chitra Govind Rajput. Formulation and Evaluation of Fenugreek powder as Nutraceutical from seeds of Trigonella foenum graecum. Research Journal of Pharmacognosy and Phytochemistry. Res. J. Pharmacognosy and Phytochem. 2021; 13(2):78-80. DOI: 10.52711/0975-4385.2021.00013.

37. Raghavendra Rao NG, Durga Bhavani, Shwetha.  Design and Evaluation of Valsartan Fast dissolving Tablets by Direct Compression Method. Indo-American Journal of Pharm Research. IAJPR:2015:5(01)158-168.

 

Accepted on 29.07.2022           © RJPT All right reserved

Research J. Pharm. and Tech 2023; 16(1):23-30.