INTRODUCTION:

Recently pharmaceutical preparations used for elderly patients have been investigated to improve the treatment compliances and quality of life of patients¹. Recent advances in Novel Drug Delivery System (NDDS) aims to enhance safety and efficacy of drug molecule by formulating a convenient dosage form for administration and to achieve better patient compliance. One such approach is “Mouth Dissolving Tablet”^2,3. Taste of the medicament is one of the important characteristic of orodispersible tablet. As most drugs are unpalatable, this delivery system usually contains the medicament in taste masked form which dissolves or disintegrates in patient’s mouth, thus releasing the active ingredients which come in contact with the taste buds^4,5.

Taste masking is an essential requirement for orodispersible tablets for commercial success. Ion exchange resins are water-insoluble, cross-linked polymers containing salt forming groups in repeating positions on the polymer chain⁶. Ion exchange resins are used in the drug formulations to stabilize the sensitive components, sustain release of drug, disintegrate tablets, and mask taste⁷. Drug release from the drug resin complex depends on the ionic environment (i.e. pH and electrolyte concentration) within the gastrointestinal tract, as well as the properties of the resin. Drug molecules are released by exchanging with appropriately charged ions in the gastrointestinal tract followed by diffusion of free drug molecule out of the resin^8,9.

Strong acid cation resins (sulfonated styrenedivinylbezene copolymer product) function throughout the entire pH range and can be used for masking the taste of basic drugs. Weak acid cation exchange resins function at pH values above 6.0. Similarly, strong base anion-exchange resins function throughout the entire pH range and can be used for masking the taste of acidic drugs, while the weak base anion exchange resins function well below pH 7.0¹⁰.

Overactive bladder is a common condition that significantly impacts overall quality of life¹¹. Mirabegron is a new beta-3 adrenoreceptor agonist which causes detrusor smooth muscle relaxation and has been proposed to be effective for treating overactive bladder symptoms. However, mirabegron has a very strong bitter taste and it is necessary to mask the bitter taste in order to formulate orodispersible tablets¹².

In the present work an attempt has been made for formulating orodispersible tablets of taste- masked mirabegron resinate. A tasteless, directly compressible, stable resinate of bitter tasting mirabegron was made by using strong cation exchange resin, Tulsion 344. Process for preparing, isolating and characterizing the tasteless complex of bitter tasting drug and process for producing the orodispersible tablet formulation was also studied.

MATERIALS AND METHODS:

Mirabegron was obtained as a gift sample from Micro Labs (Bangalore, India). Tulsion 344 was obtained as gift sample from Thermax India (Pune, India) Ac-Di-Sol (NMT 2% retained # 200, NMT 10% retained #325) was obtained from wockhardt Research Centre (Aurangabad, India) Other AR grade chemicals were purchased.

Selection of Resin:

For the acidic drugs anion exchange resins are used and for the basic drugs, cation exchange resins are used. Since mirabegron dissociation constant (pKa) is 4.5 and 8.0 a strong cation exchange resin Tulsion 344 (sodium polystyrene sulphonate) was selected for effective drug loading and bitter taste masking, which works over the entire pH range.

Resinate preparation by batch method¹³:

Resinates were prepared using batch method. Drug: Resin ratios from 1:1 to 1:3 were prepared. An accurately weighed amount of activated resin particles were suspended in demineralised water for 30 min in a beaker containing 50ml of demineralised water to allow uniform swelling of polymer, after which the drug was added slowly under stirring conditions. The stirring was continued for 2 hrs. The mixture was kept aside to allow the particles to settle down and was then filtered through whatman filter paper no. 41 and washed with 50ml of demineralised water to remove the free drug. The amount of free drug in the filtrate was measured spectrophotometrically at 251nm with suitable dilutions. The difference between initial amount of mirabegron and content of collective filtrate gave amount of drug bound to resin.

Optimization of various parameters for maximum drug loading:

Purification/Activation of Ion Exchange Resin Tulsion 344, 1gram placed on a Whatman filter paper in a funnel, was washed with distilled water. The wet resin was activated by 1N HCl (100ml) followed by washing with distilled water and was dried overnight in hot air oven at 50⁰C and was stored in an air tight glass container. Resinate was prepared in the same way as discussed earlier using 1gram of mirabegron and acid –activated resin. Similarly alkali activation of Tulsion 344 using 1 N NaOH was done. Tulsion 344 was also activated with combined treatment of 1N HCl and 1N NaOH solutions. Drug loading in each case was determined.

Effect of soaking time:

Selected resin was soaked in 25ml of deionised water for 10, 30, 40, 60, 90 and 120 min. Accurately weighed quantity of mirabegron (as per 1:2 ratio) was added to previously soaked resins. The solutions were stirred for 1 hr. The mixtures were filtered through whatman filter paper no. 41 and unbound drug in the filtrate was estimated spectrophotometrically at 251nm.

Effect of temperature:

Selected resin was soaked in 25ml of deionised water for 30 min. Accurately weighed quantity of mirabegron (as per 1:2 ratio) was added to previously soaked resins. The solutions were stirred for 120 min at 10, 20, 30, 40 and 50⁰C. The mixtures were filtered and whatman filter paper no. 41 and unbound drug in the filtrate was estimated spectrophotometrically at 251nm.

Effect of pH:

Accurately weighed quantity of mirabegron (as per 1:2 ratio) was added to selected resin that was soaked in 25 ml of solution of pH 2, 3, 4, 5, 6, 7 and 8 using standard solutions of hydrochloric acid and sodium hydroxide. The solutions were stirred for 1 hr. The mixtures were filtered through Whatman filter paper no. 41 and unbound drug in the filtrate was estimated spectrophotometrically at 251nm.

Effect of stirring time:

Selected resin was soaked in 25ml of demineralised water for 30 min. Accurately weighed quantity of mirabegron (as per 1:2 ratio) was added to previously soaked resin. The solutions were stirred for 10, 30, 60, 90, 120 and 150 min. The mixtures were filtered through Whatman filter paper no. 41 and unbound drug in the filtrate was estimated spectrophotometrically at 251nm.

Characterization and Evaluation of Taste Masked Resinates:

Fourier transform infra-red spectroscopy:

The drug, resin and resinate were subjected to Fourier Transform Infra-Red (FTIR) studies to check drug resin interaction using FTIR (Shimadzu 8400 s). The potassium bromide (KBr) disk method was used for preparation of sample. The data was compared with the standard spectrum for mirabegron and the characteristic peaks associated with specific structural characteristics of the molecule and their presences/absences in the resin as well as complex were noted. The IR spectra of the complex showed that there was no interaction between drug and resin. Peaks of both drug as well as resin were observed and interpreted.

Differential scanning calorimetry:

The thermal behaviour of mirabegron, tulsion 344, physical mixture of mirabegron and tulsion 344 and mirabegron: tulsion 344 complex were examined by DSC by using DSC 60 Shimadzu model to confirm complexation. Approximately 10.0mg of sample was loaded into an aluminium pan, hermatically sealed under nitrogen and run at scanning rate of 15⁰C/min over a temperature range of 40⁰ to 240⁰ in a dynamic nitrogen atmosphere. An empty sealed aluminium pan was used as a reference.

In-vivo evaluation for taste masking¹⁴:

Taste of resinate was checked by time intensity method. The healthy human volunteers were used for taste masking and informed consent was obtained from all of them. Bitterness was measured by consensus of a trained taste panel, with 20mg of sample held in the mouth for 5 to 10 sec., than spat out: the bitterness level was then recorded. A numerical scale was used with the following values:

0.0 = tasteless, 1.0 = acceptable bitterness, 2.0 = slight bitterness, 3.0 = moderately bitterness 4.0 = strong bitterness.

These volunteers were instructed not to swallow the granules, which were placed on the tongue. They were instructed to thoroughly gargle their mouth with distilled water after the completion of test.

Determination of drug content in the resinate:

Resinate so prepared by the batch process, was evaluated for the drug content. 50mg of resinate was stirred with 50ml of acidic buffer (pH 1.2) till the entire drug was leached out. Then the suspension was filtered and further dilutions were made. The drug content was noted spectrometrically at 251nm using acidic buffer (pH 1.2) as blank.

Rheological characterization:

Angle of repose (θ)¹⁵

It is the maximum angle possible between the surface of pile of powder and the horizontal plane. Angle of repose is calculated by fixed funnel method using following equation.

θ = tan ^-1(h/r) ------------- (1)

Where, h = height of pile, r = radius of pile.

Bulk Density¹⁶:

The bulk density was calculated using following equations:

Wt. of resinate

Poured Density = ------------------------- ---------(2)

Bulk vol. of

Wt. of resinate

Tapped Density =------------------------- ---------(3)

Tapped vol. of resinate

Tapped Density – Poured Density

% Compressibility = ------------------------ x 100 -----(4)

index (CI) Tapped Density

Tapped Density

Hausner’s Ratio =------------------------------- ---(5)

Poured Density

In- Vitro Release Study of Drug: Resin (1:2) complex¹⁶:

Resinate prepared in 1:2 (drug: resin) ratios at pH 7 was subjected to dissolution in acidic buffer pH 1.2¹⁸. 25mg of drug equivalent resinate was placed in the dissolution flask. The dissolution medium was 900ml of acidic buffer maintained at 37⁰C+0.5⁰C. The paddle was rotated at 100rpm. The sample (5ml) was withdrawn at suitable time intervals and its absorbance was measured at 251nm.

Formulation of orodispersible tablets by direct compression:

Direct Compression is the easiest and cheapest tableting approach¹⁷. Orodispersible tablets of mirabegron: resin complex were prepared using direct compression method after incorporating superdisintegrants such as crosscarmellose sodium (Ac-Di-Sol) in different concentrations. Three formulations of mirabegron: resin complex were prepared. Resinate, mannitol (Perteck M) and microcrystalline cellulose (Avicel PH 101) were mixed thoroughly in a glass mortar using a pestle. Superdisintegrant was incorporated in the powder mixture, aspartame (sweetening agent), flavour (strawberry flavour), menthol were added to enhance the palatability of tablet and finally aerosil was added as lubricant. The mixture was weighed, die cavity for tablet machine was set for 170 mg, and then the tablet was compressed using 7mm round flat faced punch of rotary tablet machine (Karnavati, India). Compression force was kept constant for all formulations.

Evaluation of orodispersible tablets:

Weight variation test¹⁸:

The 20 tablets were selected randomly from each formulation and weighed individually to check for weight variation as per USP.

Hardness and Friability¹⁹:

The hardness of the tablets was determined using Monsanto Hardness tester. It is expressed in Kg/cm². Three tablets were randomly picked from each formulation and the mean and standard deviation values were calculated. The friabilator was operated at 25rpm for 4 minutes or run up to 100 revolutions. The tablets were weighed again. The percentage friability was then calculated. % Friability of tablets less than 1% is considered acceptable.

Wetting Time²⁰:

A piece of tissue paper folded twice was placed in a small petry dish (ID6.5cm) containing 6ml of pH6.8 (simulated saliva fluid). A tablet was put on the paper, and the time for complete wetting was measured. Three trials for each were performed.

Mouth Feel²¹:

To know the mouth feel of the tablets, the same human volunteers held the disintegrated particles in the mouth for 30 seconds and the taste sensation felt was recorded.

In Vivo Disintegration Time:

Six healthy human volunteers, whose informed consent was first obtained, were selected for the study. Each volunteer randomly took one tablet from each formulation and kept on the tongue. Time taken for complete disintegration of the tablet on the tongue was noted. It was expressed in seconds. These volunteers were instructed not to swallow the disintegrated mass of the tablet and thoroughly gargle their mouth with distilled water after the completion of test. 3 trials were performed at different time intervals.

In Vitro Dispersion Time¹⁸ (USP NF 2000):

Three tablets from each formulation were randomly selected. In vitro dispersion time was measured by dropping tablets in a measuring cylinder containing 6ml of pH 6.8 (simulated saliva fluid)

In vitro release profile of formulated tablets:

Dissolution test of tablets was performed using acidic buffer pH 1.2 with USP dissolution type II apparatus at 100 rpm and 37±0.5⁰C temperatures. Test sample (5 ml) was withdrawal at particular time interval and replaced with fresh dissolution media maintained at 37±0.5 ⁰C. The test sample was filtered (membrane filter, 0.45μm) and analyzed using UV spectrophotometer atλ_max251 nm. This test was performed on 3 tablets and mean ± SD calculated.

RESULTS AND DISCUSSION:

Loading of mirabegron on Tulsion 344 was carried out by batch process. Complexation between drug and resin is essentially a process of diffusion of ions between the resin and surrounding drug solution. Tulsion 344 had fine particle size with high swelling efficiency made it suitable for batch process by providing more surface area for exchange of ions rather than column process.

Optimization of various parameters for maximum drug loading:

Combined acid and alkali treatment may purify the resin by removing adsorbed impurities associated with industrial scale manufacture and hence showed maximum drug loading upto 96.78±0.62%. whereas inactivated resin showed 85.64±1.20%. Resin activated with 1N HCl and 1N NaOH showed 91.02±1.05% and 93.12±1.31% respectively.

For the selection of the proper drug resin ratio, the ratio of the drug resin was varied, keeping concentration of drug constant. The results showed that drug resin in the ratio of 1:2 has better drug loading of 97.08±0.18 as compared to ratio 1:1 which showed 63.50±0.68 and ratio 1:2 showed 98.43±0.39.

Soaking of resin increases the rate and extent of ion exchange process. In non-soaked condition the exchangeable groups are latent and coiled in the resin matrix. Soaking increases swelling and in turns the surface area for orientation of exchangeable groups towards outside. Soaking time of 30 min was optimized for maximum drug loading process showing 90.38±1.35 % drug bound to resin. While soaking time of 10 mins was found to give 81.00±1.01, 40 mins 90.52±0.67, 60 mins. 91.04±1.42, 90 mins 91.84±0.98% drug bound to resin.

The loading of Mirabegron onto ion exchange resin is equilibrium process, which depends upon the presence of, cationic form of the drug in the solutions. The presence of cationic form of drug is influenced by pH of the solution, which therefore exerts an influence on loading efficiency. After activation with acid and alkali treatment, the exchangeable ion on the resin is H⁺. Relative selectivity of H⁺ is less than other ionic forms, and therefore it increases percent complexation. Maximum drug loading occurs at pH near neutral i.e pH 7 shown 96.84±0.98% drug bound. This may be due to fact that the fraction of mirabegron (pKa 4.5 and 8.0) protonation is less at acidic and basic pH and reduces interaction with resin at pH extremities.

The effect of mixing time on drug loading showed that, the percentage of drug bound to resin was found to increase as the mixing time increased, as shown in the table. The result showed that maximum binding of 97.14±0.89 occurred in approximately 2 hours.

Effect of temperature on drug loading was not very significant. Hence, the operational temperature was selected for further study.

Evaluation Of Taste Masked Resinates:

Fourier Transform Infra-Red Spectroscopy:

FTIR spectrum of the drug mirabegron, tulsion 344 and mirabegron: tulsion 344 resinate were as shown in the figure 1, 2 and 3.

The IR spectrum of mirabegron showed N-H stretching of amide at 3350.04 cm^‑1_,-C=O at 1649.71, aliphatic C-H stretching at 2849.50, -C-N stretching at 1259.10 of primary aromatic amine. The peaks corresponding to C-H stretching and -C-N stretching disappeared in IR spectrum of resinate confirms the complex formation of drug with resin.

Figure 3: FTIR spectra of mirabegron: tulsion complex

Differential Scanning Calorimetry:

DSC studies revealed some information on solid-state interactions between drug and ion exchange resin. The DSC thermograms of pure components, and of the different drug-ion exchange resin systems are presented in following figures 4. The DSC curve of mirabegron was typical of a crystalline anhydrous substance, with a sharp endothermic peak at 138.62⁰C. Tulsion 344 exhibited broad endothermic asymmetrical peak between 110-126⁰C with melting point at 118.35⁰C. DSC thermogram of resin tulsion 344 showed two endotherm of fusion. However, the characteristic thermal peak of the drug shifted to 240.67⁰C temperature, but strongly reduced in intensity, in the drug-resin complex form. The shift in melting point and reduction of the intensity of endothermic peak exhibited by resinate confirming the complex formation between drug and resin.

Fig.4. DSC spectra of mirabegron, resinate of mirabegron-tulsion (1:2) and tulsion 344

In-vivo evaluation for taste masking:

Evaluation of taste of resinate was carried out using time intensity method and by using panel of human volunteers.

Table 1: Bitterness Evaluation by Taste Panel

	1	2	3	4	5	6
Pure drug	4.0	4.0	4.0	4.0	4.0	4.0
Adsorbate (5 sec.)	2.0	0.0	0.0	1.0	0.0	0.0
Adsorbate (10 sec.)	1.0	0.0	0.0	0.0	0.0	0.0

0.0 = tasteless, 1.0 = acceptable bitterness, 2.0 = slight bitterness, 3.0 = moderately bitterness, 4.0 = strong bitterness.

Determination of Drug Content in the Resinate:

In- Vitro Release Study of Drug: Resin (1:2) complex:

Dissolution of resinate was carried out to observe the release of the drug in resinate. A similar condition as that of stomach (Acidic Buffer pH 1.2) was employed in dissolution apparatus. Results indicate that more than 90% of drug was released in 45 minutes, and total drug was released in 60 minutes.

Formulation of [Bitterless] Orodispersible Tablet of Mirabegron-Tulsion 344 Complexes

Formulations and Evaluations of Orodispersible Tablets:

170 mg tablet was prepared by using drug-resin complex equivalent to 25mg of mirabegron, Avicel PH101, Aspartame, Pineapple flavor, Menthol, Aerosil and Croscarmellose as Superdisintegrant. Three formulations viz. F1 to F3 of Mirabegron –Tulsion 344 complex were prepared by using Croscarmellose sodium in 6.0%, 8.0%, and 10.0% keeping tablet weight 170mg and the formulations are summarized in Table No. 3 Formulated tablets of Mirabegron –Tulsion 344 complex were evaluated for different tests. Formulation F3 show the fast disintegration and fast dissolution of tablets than other formulations.

Table 2: In Vitro Release of mirabegron from the Drug Resin Complex

Time Min.	Abs.(nm)	Conc.(µg/ml)	Conc.(mg/5ml)	Conc.(mg/900ml)	Cumulative Drug release	Cumulative %Drug release
0	0	0	0	0	0	0
5	0.187	1.853	0.093	16.681	16.681	66.725
10	0.215	2.129	0.106	19.158	19.251	77.004
15	0.231	2.289	0.114	20.602	20.708	82.834
30	0.253	2.508	0.125	22.571	22.686	90.743
45	0.274	2.710	0.135	24.389	24.515	98.058
60	0.279	2.762	0.138	24.861	24.997	99.988

Pharmacotechnical Characterization:

Rheological properties of tablet blend:

Angle of Repose of tablet blend was found to be 27.54⁰. The value of bulk density was 0.7843gm/cm³ showing good packing property. Carr’s compressibility index was 12.8±1.34 and Hausner ratio 1.17±1.12. Thus it can be concluded that the blend exhibit good flow.

Table 4: Evaluation of Orodispersible Tablets of Drug Resin Complex

Test	F1	F2	F3
Weight variation test	170.0±1.4	170.4±1.2	170.2±1.6
Hardness (Kg/cm²)	3.5±0.09	3.75±0.08	4.00±0.10
Friability (%)	0.84	0.80	0.72
Drug content (%)	100.8±0.20	100.6±0.56	99.90±0.10
Wetting time (Seconds)	45±1.00	37±1.53	30±2.00
Mouth feel	-	-	-
*In vivo* disintegration time (Seconds)	57±1.97	48±1.86	30±1.37
*In vitro* dispersion time (Seconds)	42±1.00	38±2.00	25±1.53

Mouth feel: ++ Strong bitter, + slight bitter, - no bitter

Dissolution of (bitterless) Orodispersible Tablets:

The dissolution of tablets was carried out to observe the release of the drug from the tablet. The dissolution medium was 900ml of acidic buffer (pH1.2) maintained at 37+0.5⁰C temperature. The paddle type dissolution test apparatus was used.

Table 5: In Vitro Release of Orodispersible Tablets of Mirabegron: Tulsion 344 Complex

Time (Min)	F1	F2	F3
0	0	0	0
1	11.06 ± 0.70	16.31 ± 0.61	27.56 ± 0.54
2	18.37 ± 0.91	25.90 ± 1.01	41.99 ± 0.95
3	20.72 ± 1.28	35.54 ± 1.24	58.76 ± 1.31
4	24.58 ± 1.54	43.74 ± 1.34	67.36 ± 1.54
5	31.47 ± 1.61	48.48 ± 1.51	77.75 ± 1.37
6	41.89 ± 1.34	64.49 ± 1.31	87.42 ± 1.67
7	48.87 ± 1.47	73.09 ± 2.03	100.9 ± 1.84
8	57.39 ± 1.34	86.74±2.61	-
9	67.70 ± 1.41	100.9 ± 2.87	-
10	77.57 ± 2.04	-	-
11	92.99 ± 2.14	-	-
12	99.74 ± 2.24	-	-
13	100.6 ± 1.84	-	-

Figure 5: Dissolution profile for formulation F1, F2, F3

CONCLUSION:

The use of ion exchange resin Tulsion 344 successfully masked the bitterness of mirabegron. The resin used has added advantage of fast disintegration and direct compression property which aids the development of patient friendly orodispersible tablets.

CONFLICTS OF INTEREST:

There are no conflicts of interest.

REFERENCES:

1. Pagar HB et al. Taste Masking: A Review. Research Journal of Pharmacy and Technology. 2012; 5(2): 152-157.

2. Chang RK et al. Fast-dissolving tablets. Pharmaceutical Technology. 2000; 24(6): 52-52.

3. Malaak, FA et al. Orodispersible Tablets: Novel Strategies and future challenges in Drug Delivery. Research Journal of Pharmacy and Technology. 2019; 12(11): 5575-5582.

4. Dobetti L. Fast-melting tablets: Developments and Technologies. Pharmaceutical Technology (2001): 44-44.

5. Siddiqui et al. Fast dissolving tablets: preparation, characterization and evaluation: an overview. International Journal of Pharmaceutical Sciences Review and Research. 2010; 4(2): 87-96.

6. SOHI H, Sultana Y, Khar R. 2004. Taste Masking Technologies in Oral Pharmaceuticals: Recent Developments and Approaches. Drug Dev. Ind. Pharm.2004; 30(5): 429-448.

7. Agarwal R Rohit M, Amarjit S. Studies of ion-exchange resin complex of chloroquine phosphate. Drug Development and Industrial Pharmacy. 2000; 26(7): 773-776.

8. Manek SP Kamat VS. Evaluation of Indion CRP-244 and CRP-254 as sustained release and taste masking agents. Indian J. Pharm. Sci. 1981; 43(11-12): 209-212.

9. Honeysett RA et al. Taste-masked Buflomedil preparation. Eur. Pat. Appl. EP0501763. 1992.

10. Amita N, Garg S. An update on taste masking technologies for oral pharmaceuticals. Indian Journal of Pharmaceutical Sciences. 2002; 64(1): 10.

11. Bhide AA et al. Mirabegron–a selective β3-adrenoreceptor agonist for the treatment of overactive bladder. Research and Reports in Urology. 2012: 41.

12. Kasashima Y et al. 2015. U.S. Patent Application No. 14/388,099.

13. Tejas K, Deshmukh G. A Review on Orodispersible Tablets: A Novel Approach. Research Journal of Pharmacy and Technology. 2019; 12(8): 3993-4001.

14. Borodkin S , Dean PS. Polycarboxylic acid ion‐exchange resin adsorbates for taste coverage in chewable tablets. Journal of Pharmaceutical Sciences.1971; 60(10): 1523-1527.

15. Aulton ME, Taylor K. Pharmaceutics-The science of dosage form design, Churchill Livingstone. London, England. 2002: 340-348.

16. Martin A. Physical Pharmacy: Physical Chemical Principles in the Pharmaceutical Sciences. BI Waverly. Pvt Ltd, 1993.

17. More SA and Shrinivas KM. Formulation Development and Evaluation of Orodispersible Tablet of Omeprazole by Using Co-Processed Superdisintegrant. Research Journal of Pharmaceutical Dosage Forms and Technology. 2012; 4(4): 216-220.

18. Cohen JL. The Official compendia of standards. The United States Pharmacopeia (USP 24 NF 19). The United States Pharmocopedial Convention Press, 1975.

19. Das PS and Puja S. Development and Optimization of Orodispersible Tablets of Serotonin Hydrochloride. Research Journal of Pharmaceutical Dosage Forms and Technology. 2018; 10(1): 13-16.

20. Redkar MR, Gore SP, Devrajan PV. D-Zolv: Taste masked mouth dissolving tablet. Indian J Pharm Sci. 2002; 64(3): 291-292.

21. Sahu SK et al. Formulation and evaluation of orodispersible tablet of montelukast sodium. Research Journal of Pharmacy and Technology. 2018; 11(3): 1112-1118.

Received on 10.08.2020 Modified on 06.09.2020

Research J. Pharm. and Tech. 2021; 14(9):4736-4742.

DOI: 10.52711/0974-360X.2021.00824

Ingredients (Quantity in mg.)	F1	F2	F 3
Resinate (Equivalent to 25mg of Mirabegron)	76.50	76.50	76.50
Perteck-M	45.57	42.17	38.77
Avicel PH 101	30.36	30.36	30.36
Crosscarmellose Sodium [Ac Di Sol]	10.20	13.60	17.00
Aerosil	0.625	0.625	0.625
Aspartame	3.125	3.125	3.125
Menthol	0.50	0.50	0.50
Strawberry Flavor	3.125	3.125	3.125
Tablet Weight	170	170	170

Table 3: Formulation of Orodispersible Tablets of Mirabegron: Tulsion 344 Complex

Ingredients (Quantity in mg.)

F1

F2

F 3

Resinate (Equivalent to 25mg of Mirabegron)

76.50

76.50

76.50

Perteck-M

45.57

42.17

38.77

Avicel PH 101

30.36

30.36

30.36

Crosscarmellose Sodium [Ac Di Sol]

10.20

13.60

17.00

Aerosil

0.625

0.625

0.625

Aspartame

3.125

3.125

3.125

Menthol

0.50

0.50

0.50

Strawberry Flavor

3.125

3.125

3.125

Tablet Weight

170

170

170

Table 4: Evaluation of Orodispersible Tablets of Drug Resin Complex