INTRODUCTION:

In 2004, United States Food and Drug Administration (USFDA) approved Solifenacin Succinate tablets 5 mg and 10 mg brand named VESICARE^® manufactured by Astellas for the treatment of overactive bladder. In 2020, USFDA approved Solifenacin Succinate oral suspension 1mg/ml brand named VESICARE LS^®manufactured by Astellas for the treatment of neurogenic detrusor overactivity in pediatric patients aged 2 years and older.¹ The average unit price of the tablet is 13 US dollars and and suspension bottle is 275 US dollars.

In India as of June, 2021, 12 companies viz. Dr. Reddys, Sun Pharma, Lupin, Cipla, Hetero, MSN, Alembic, TAS, Samarth, Redmed, Fourrts and Micro labs are involved in the manufacturing of Solifenacin Succinate Tablets, 5mg and 10mg. The configuration is 10 to 15 tablets in unit dose packing. The average unit price of the tablet is in range of 33 to 53 Indian rupees^2-3. There is no oral suspension product available for Solifenacin Succinate in India. Overactive bladder is a common problem that creates both physical and psychological nuisance with widespread human and social implications causing discomfort, shame, and loss of self-confidence^4-6. In males, Cigarette smoking and tobacco chewing has been shown to have a positive association with Overactive bladder^7-9. Overactive bladder problem is twice more common in females as compared to males^10-12. As of 2021 statistics, in India 1 in 3 Women suffer from Overactive bladder due to stress^13-15. Also the alarming fact is 40-55% of affected Women doesn’t turn-up for medical intervention due to social stigma^16-18. Neurogenic detursor overactivity– an overactive bladder issue has a prevalence of 15–20% of the pediatric population¹⁹^-22.

Akio Sugihara et.al (2011)²³ prepared Solifenacin Succinate film coated tablets by aqueous wet granulation process. Since the international brand product doesn’t have Polyethylene glycol 6000 as part of core tablet but has Polyethylene Glycol 8000 in coating; the reason for addition of Polyethylene Glycol 6000 and its effect on stability in this cited research work is vague. The elaboration on crystallinity & amorphism solid-state stability of Solifenacin Succinate needs further substantiation. Ananda Kumar et.al (2013)²⁴ prepared Solifenacin Succinate uncoated tablets 5 mg by aqueous wet granulation process. The finalized composition was not stability evaluated. The marketed brand product is available as coated tablet but the cited research work is an uncoated tablet. Suh Young Hee et.al (2015)²⁵ prepared Solifenacin Succinate film coated tablets, 5 mg by direct blending and compression process. Since the international brand product doesn’t have anti-oxidant as part of composition the reason for addition and its effect on stability is vague. The elaboration on crystallinity & amorphism solid-state stability of Solifenacin Succinate needs further substantiation. Naga Sudha et.al (2015)²⁶ prepared Solifenacin Succinate uncoated tablets by direct blending and compression process. The dissolution profile of the finalized composition – uncoated tablet is not comparable to the brand product which is a film-coated tablet. Hari Prasad Bhatta et al (2016)²⁷ prepared Solifenacin Succinate uncoated tablet by direct blending and compression process. The finalized composition was not stability evaluated. The marketed brand product is available as coated tablet but the cited research work is an uncoated tablet.

The objective of the present research is to develop a commercially feasible and cost-effective tablet and oral suspension of Solifenacin Succinate for Indian market with quality and stability comparable to the International brand product.

MATERIALS AND METHODS:

Solifenacin Succinate was from Divis Labs, India. All the excipients, reagents, salts, solvents were of compendial grade. Samples analysis was done in-house method based on the analytical method reported in literatures^28-42Pharmacopoeial general chapters followed for the characterization and evaluation of In-process samples⁴³.

RESULTS AND DISCUSSION:

A) Characterization of Active Pharmaceutical Ingredient (API):

The characterization details of Active Pharmaceutical Ingredient viz. Particle Size Distribution by Malvern and Angle of Repose for flow determination is provided below,

Particle Size Distribution (By Malvern Mastersizer): d10: 2 microns, d50: 7 microns and d90: 20 microns.

Angle of Repose: 35°.

From the API characterization details it’s evident that though the particle size distribution showing micronized grade, the material flow as inferred from angle of repose is good enough for a direct blending and compression process.

B) Characterization of Brand product:

The brand product was characterized with respect to Physico-chemical and Packing configuration which is provided in Table.1 and Table.2.

Based on table.1 details it’s clear that Brand product tablets of both strengths have the same tablet weight of 150 mg. The tablets are film-coated. Unlike reported in the literature review, there are no special excipients in composition to improve the stability. Lactose Monohydrate is used as diluent. Corn Starch as binder/disintegrant. Magnesium Stearate as lubricant. Hypromellose as film former. Polyethylene Glycol as plasticizer. Titanium Dioxide as Opacifier. Color pigment for colors. In this research, dimension aspects of tablet are kept similar to the brand product. The dissolution profile of the brand product is rapidly dissolving type. Hence in this research, the composition and process was designed to achieve comparable dissolution profile with the brand product.

Based on table.2 details it’s clear that Brand product oral suspension is made by ion-exchange resin complex using Polacrilin Potassium. Methyl Paraben and Propyl Paraben as preservatives. Propylene Glycol as solubilizer to dissolve parabens. Simethicone Emulsion 30% as antifoaming agent. Carbomer Homopolymer Type B as viscosity modifier. Xylitol and Acesulfame Potassium as sweeteners. Natural Orange Flavour as flavoring agent. Sodium Hydroxide as pH modifier for Carbomer visco-elasticity. Purified water as vehicle. The dissolution profile of the brand product is rapidly dissolving type. Hence in this research, the composition and process was designed to achieve comparable dissolution profile with the brand product.

C) Formulation and Characterization of Tablets:

The finalized composition of Solifenacin Succinate tablets 5mg and 10mg is presented in Table.3. The tablet weight of both strengths was fixed to 150mg similar to brand product. Apart from API, Starlac - a co-processed excipient of Lactose and Starch was used as diluent, binder and disintegrant. Hyqual - Magnesium Stearate was used as lubricant. To match the shade of international brand product, Opadry II 85G540089 Pink was used for coating the 10mg strength and Opadry II 85G520075 Yellow for 5mg strength. As part of preformulation study, drug-excipient compatibility was not taken up since the excipients chosen are similar to the one used in brand product. On the process part, a simple direct blending and compression process was finalized i.e. Starlac was sifted through # 25 American society for testing and materials (astm) mesh and divided into two equal parts. API was then sifted through #40 astm mesh. Hyqual was sifted through #40 astm mesh. In a double cone blender, 1^st divided part of sifted Starlac portion was loaded followed by sifted API portion then finally the remaining portion of sifted Starlac was added and blended at 15 rotations per minute (rpm) for 10 minutes. Then the blended material was sifted through #25 astm mesh and blended again at 15rpm for 15 minutes. Finally the blend was lubricated with sifted Hyqual – Magnesium Stearate at 15rpm for 5min. The blend was compressed into tablets using 7.5 mm round shaped punch tooling in a tablet press.

Table. 3 Composition of Solifenacin Succinate Tablet

Ingredients in mg per tablet	5mg	10mg
Solifenacin Succinate	5	10
Starlac	144	139
Magnesium Stearate	1	1
Opadry II 85G520075 Yellow	3.75	-
Opadry II 85G540089 Pink	-	3.75
Purified Water (Solvent for coating)	Quantity Sufficient to 18% w/w solids	Quantity Sufficient to 18% w/w solids

The core tablets were then coated in a fully perforated coating pan as per Colorcon datasheet⁴⁴. The coated tablets were then packed in High density polyethylene bottle with Polypropylene child resistant closures and stability evaluated at 40°C/75% RH for 6 months. Various testing done during blending, compression, coating and on stability is presented in Table.4.

The composition of Solifenacin Succinate tablets was kept simple. Starlac was used as a major excipient. With Starlac and drug having good flow, a direct blending and compression process was finalized. Blend uniformity, density and flow of final lubricated blend were good. During compression in a 37 station double rotary press, no tablet defects observed and the weight variation, hardness achievability, content uniformity as by uniformity of dosage units, disintegration time and friability aspects were found optimum for both strengths at turret speed of 55RPM. The prepared tablets were coated with Opadry II film coating upto 2.5% coating buildup. No defects observed in the coated tablets. The disintegration time and % dissolution of the coated tablets are comparable to the brand product. The coated tablets were packed in bottle and strip pack and evaluated for stability study at 40°C/75% RH for 6 months. Though there is a reduction in assay on stability, the % reduction is within 5% of the initial assay. In case of related substances the % degradation - the Highest Unknown Impurity is more in strip pack than the bottle but the % Highest Unknown observed in both packs were within the ICH (International Conference on Harmonization) limit of NMT 0.2%. There is no drop in % dissolution on stability and is comparable to the brand product in both the packs.

Table. 4 Characterization of Solifenacin Succinate Tablet

Particulars	5 mg	10 mg	Remarks
Stage: LUBRICATED BLEND
Blend Uniformity (%)	Mean: 99.1 Min: 93.7 Max: 105.8 %RSD: 6.1	Mean: 98.7 Min: 94.6 Max: 103.4 %RSD: 4.5	Post lubrication, Blend sampling was done at 10 different locations in blender.
Bulk Density (g/mL)	0.47	0.42	Post lubrication testing.
Tapped Density (g/mL)	0.67	0.61	Post lubrication testing.
Carr’s Index (%)	30	31	Post lubrication testing.
Hausner Ratio	1.43	1.45	Post lubrication testing.
Angle of Repose (°)	28	31	Post lubrication testing.
Loss On Drying (%)	3.24	2.97	Loss on drying of final lubricated blend was done in IR moisture analyzer at 105°C auto mode.
Stage: CORE TABLETS
Weight variation (mg)	149-153	150-152	Tablet weight variation observed during compression.
Thickness variation (mm)	3.35-3.43	3.33-3.42	Tablet thickness variation observed during compression.
Hardness variation (kP)	3.3-5.1	3.7-5.3	Tablet hardness variation observed during compression.
% Friability	0.23	0.28	Core tablets.
Disintegration time (min)	3-4	4-5	Core tablets.
Content Uniformity (%)	Mean: 98.9 Min: 96.1 Max: 103.2 %RSD: 3.1	Mean: 99.6 Min: 97.9 Max: 102.1 %RSD: 1.8	Uniformity of Dosage Units of Core tablets; Complying to limit ‘L1’ less than 15.
Stage: COATED TABLETS
Weight variation (mg)	154-159	153-157	Tablet weight variation observed post coating.
Assay (%)	99.3	98.7	Coated tablets.
Highest Unknown Impurity (%) Total Impurity (%)	0.03 0.11	0.01 0.13	Coated tablets. Highest Unknown limit: Not more than 0.2% Total Impurity limit: Not more than 1%
Water by Kf (%)	5.42	5.19	Coated tablets.
Disintegration time (min)	6-7	7-8	Coated tablets.
Dissolution	87-91% in 15 min	86-92% in 15 min	Coated tablets dissolution tested in 900 mL, Purified Water using USP-II (Paddle), 50 RPM.
Stage: 40°C / 75% RH – 6^th MONTH in High density polyethylene bottle with Polypropylene child resistant closure
Assay (%)	97.5	97.9	Coated tablets on stability in bottle pack.
Highest Unknown Impurity (%) Total Impurity (%)	0.09 0.34	0.07 0.39	Coated tablets on stability in bottle pack.
Water by Kf (%)	5.58	5.27	Coated tablets on stability in bottle pack.
Disintegration time (min)	7-8	7-8	Coated tablets on stability in bottle pack.
Dissolution	90-93% in 15 min	88-95% in 15 min	Coated tablets on accelerated stability study in bottle pack.
Stage: 40°C / 75% RH – 6^th MONTH in Strip packing
Assay (%)	95.3	94.1	Coated tablets on stability in strip pack.
Highest Unknown Impurity (%) Total Impurity (%)	0.16 0.65	0.12 0.51	Coated tablets on stability in strip pack.
Water by Kf (%)	5.91	5.97	Coated tablets on stability in strip pack.
Disintegration time (min)	9-10	10-11	Coated tablets on stability in strip pack.
Dissolution	84-90% in 15 min	85-89% in 15 min	Coated tablets on accelerated stability study in strip pack.

Table. 5 Composition and Characterization of Oral Suspension

Composition of Oral Suspension
Solifenacin Succinate Tablets, 10 mg	15 Tablets
Ora-Plus & Ora-Sweet (1:1)	Quantity sufficient to 150mL
Characterization of Oral Suspension
Particulars	Solifenacin Succinate Oral Suspension
Label Claim	Oral suspension containing 1 mg /mL of Solifenacin Succinate equivalent to 0.75 mg / mL of Solifenacin
Description	Light pink colored suspension
pH	4-5
Viscosity	500–600 cps
Osmolality	800-1000 mOsm/Kg
Assay	100.1%
Highest Unknown Impurity (%) Total Impurity (%)	0.01 0.11
Microbial Load	Absent
Organoleptics	Palatable
% Average Dissolution	100.3% in 15 min using USP-II (Paddle), 50 RPM, 900 mL, Purified Water
Redispersibility	Readily redispersible on shaking before use
Stage: 2-8°C– 90 days in intended packing configuration
Description	Light pink colored suspension
pH	4-5
Viscosity	500–600 cps
Osmolality	800-1000 mOsm/Kg
Assay	98.7 %
Highest Unknown Impurity (%) Total Impurity (%)	0.05 0.17
Microbial Load	Absent
Organoleptics	Palatable
% Average Dissolution	99.7 % in 15 min using USP-II (Paddle), 50 RPM, 900 mL, Purified Water
Redispersibility	Readily redispersible on shaking before use

D) Formulation and Characterization of Oral Suspension:

Tablets was placed in a mortar, and comminuted to a fine powder. The powder was wetted with 30mL Ora-Plus and Ora-Sweet⁴⁵, and triturated to a smooth paste. 60 mL of Ora-Plus and Ora-Sweet was added to the mortar and mixed to a pourable consistency. The contents were transferred to calibrated amber polyethylene terephthalate (PET) bottles. Finally the volume was made up to 150mL with Ora-Plus and Ora-Sweet and mixed well. The compounded suspension bottle was capped with child-resistant high-density polyethylene-polypropylene caps with a pulp and vinyl seal liner and stability evaluated at 2-8°C for 90 days. Details are presented in Table.5. From table.5 it’s evident that the oral suspension of Solifenacin Succinate was prepared using Solifenacin Succinate Tablets, 10 mg and Ora-Plus and Ora-Sweet (1:1) mixture. The compounded suspension was stable immediately after preparation as well as for 90 days at 2-8°C. Test on palatability, % dissolution, viscosity, osmolality, redispersibility, microbial load, assay and related substances was found comparable at initial (t0) and stability (t90).

E) Commercial feasibility and Cost-effectiveness:

The finalized formulation and process for making Solifenacin Succinate Tablets, 5mg and 10mg and Solifenacin Succinate Oral Suspension, 1mg/mL is commercially feasible and cost-effective since there is 1) less material management – API, Starlac, Magnesium Stearate, Opadry and Purified water. Within 2 hours, dispensing for a commercial batch size of 15 lakhs tablets for each strength can be completed. 2) Process-wise less cumbersome, the process train involves unit operations namely Sifting, Blending, Compression, Coating and Packing. Within 2.5 shifts (8 hours per shift) 15 lakhs batch size of a strength can be manufactured and packed in bottle and strip packs. 3) Less resource intensive – limited man-power and limited power consumption i.e. from dispensing to packing 2-3 trained personnel sufficient to complete the manufacturing-packing cycle. Since the main manufacturing doesn’t involve any granulation or drying, the process is an advantage from cost-saving and environment view point: less carbon foot-print. 4) Scaling-up - Solifenacin Succinate Tablets, 5mg and 10 mg was successful upto 15 lakhs batch size using 600 L double cone blender at 15rpm for 30 minutes; 37 station double rotary tablet press at 55RPM with output of 244,200 tablets per hour; commercial-scale fully perforated coating pan with which Opadry II coating was completed in 30 minutes; with hi-speed multi-channel strip packing and bottle packing lines running parallel the whole packing operation was completed in 2-3 hours. 5) Customized apothecary - Compounding of oral suspension can be done as and when required using the Solifenacin Succinate Tablets, 10mg. The advantage is the prepared suspension was found to be stable for 90 days from date of preparation unlike the brand product VESICARE LS^™ which is stable for 28 days from date of container opening. 6) The cost of the product with tax was calculated using Tally ERP 9 software. The unit price of the tablet is 15.34 Indian rupees for 5mg and 22.42 Indian rupees for 10mg; which is 1.5 times cheaper within India and about 50 times cheaper in International market. The unit price of the compounded oral suspension bottle of 150mL is 448.4 Indian rupees which is 46 times cheaper in International market.

CONCLUSION:

Commercially feasible and cost-effective formulation of Solifenacin Succinate Tablets, 5mg and 10mg was designed by a direct blending process with less excipients. The process was completely characterized in blend stage, compression stage as well as on stability and found comparable to VESICARE^®. The compounded oral suspension of Solifenacin Succinate 1 mg per mL was made with Solifenacin Succinate Tablets, 10mg and the formulated suspension is comparable to VESICARE LS™. From the literaturesand Freedom of information (FOI)^46-47 it’s evident that Solifenacin Succinate is a BCS Class-1 drug and the VESICARE^® tablet is bioequivalent to VESICARE LS™.

CONFLICT OF INTEREST:

The authors have no conflict of interest regarding this research.

ACKNOWLEDGEMENTS:

Authors thank Managing directors, Mr. J. Jayaseelan and Mrs. J. Bernice Sugirtha for permitting the R&D trial and commercialization.

REFERENCES:

1. https://www.accessdata.fda.gov.

2. https://www.drugs.com.

3. https://www.medplusmart.com.

4. Uma Singh. et al Prevalence and risk factors of urinary incontinence in Indian women: A hospital-based survey. Indian Journal of Urology. 2013; 29(1): 31-36. DOI: 10.4103/0970-1591.109981.

5. Aathira KA. et al Prevalence and factors of urinary incontinence among postmenopausal women attending the obstetrics and gynecology outpatient service in a tertiary health care center in Kochi, Kerala. Indian Journal of Community Medicine. 2019; 44(5): 30-33. DOI: 10.4103/ijcm.IJCM_29_19.

6. https://www.hindustantimes.com/india/50-m-suffer-from-urinary-incontinence/.

7. https://www.ics.org/Abstracts/Publish/241/000345.pdf.

8. Vishal Bansal. et al Tolerance of bladder antispasmodics in children with urinary incontinence: An observational study from North India. Indian Journal of Pharmacology. 2011; 43(6): 744-745. DOI: 10.4103/0253-7613.89847.

9. http://www.uniindia.com/one-in-three-women-suffer-from-stress-urinary-incontinence-in-their-lives-in-india/.

10. Kalyani P. et al Prevalence of urinary incontinence and its severity among women in urban Chidambaram – a cross sectional study. International Journal Of Community Medicine And Public Health. 2018;5(10):4543-47. DOI: http://dx.doi.org/10.18203/2394-6040.ijcmph20184007.

11. Bhanu Priya. et al Prevalence and risk factors of urinary incontinence among women delivering in a tertiary care center of northern india. Obstetrics & Gynecology International Journal. 2015;3(4):11-12. DOI: 10.15406/ogij.2015.03.00087.

12. Sanjay Sinha. et al The Urological Society of India survey on urinary incontinence practice patterns among urologists. Indian Journal of Urology. 2018;34(3):202-210. DOI: 10.4103/iju.IJU_85_18.

13. Bijit Biswas. et al Urinary incontinence, its risk factors, and quality of life: A study among women aged 50 years and above in a rural health facility of west bengal. Journal of Mid-life health. 2017;8(3):130-136. DOI: 10.4103/jmh.JMH_62_17.

14. Alyssa Greiman. et al Considerations in Pediatric Overactive Bladder. Textbook of Contemporary Pharmacotherapy of Overactive Bladder. 2019;231-244. DOI:10.1007/978-3-319-97265-7_14.

15. Malar Kodi Aathi. et al Understanding of Urodynamics Testing. Asian Journal of Nursing Education and Research. 2013;3(3):171-176.

16. Worlanso A. Shimray. et al Quality of life and health-seeking behavior of women with Postpartum urinary incontinence. Asian Journal of Nursing Education and Research.2020;10(3):298-304. DOI: 10.5958/2349-2996.2020.00062.2.

17. Christina Jose. et al Effectiveness of structured teaching programme on knowledge regarding pelvic floor muscle exercises in prevention of urinary incontinence among premenopausal women admitted in selected hospital Bangalore. Asian Journal of Nursing Education and Research. 2021; 11(3):307-310. DOI: 10.52711/2349-2996.2021.00074.

18. G. Jayathangaselvi. Assess the knowledge and attitude on urinary incontinence and demonstration of kegel exercise as primary prevention among women at rural community. International Journal of Nursing Education and Research. 2015;3(2):149-152.

19. R. Deepa. et al Save My Bladder. International Journal of Nursing Education and Research. 2020;8(4):483-487. Doi: 10.5958/2454-2660.2020.00106.4.

20. Yuvarani. G. et al Efficacy of Otago versus SAIL along with pelvic floor muscle strengthening exercise in avoiding urinary incontinence and fall risk among women. Research Journal of Pharmacy and Technology. 2019;12(3):1105-1110. Doi: 10.5958/0974-360X.2019.00181.1

21. Rajalaxmi. V. et al Efficacy of pelvic floor muscle training, yoga and cognitive behavioral therapy for urinary incontinence in diabetic women – a randomized controlled double binded study. Research Journal of Pharmacy and Technology. 2019; 12(10): 4618-4622. Doi: 10.5958/0974-360X.2019.00794.7

22. Pavithralochani V. et al Efficacy of kegel’s exercise vs pilates in subject with urinary incontinence during pregnancy. Research Journal of Pharmacy and Technology. 2019;12(12): 5943-5946. doi: 10.5958/0974-360X.2019.01031.X

23. Akio Sugihara. et al Composition of Solifenacin for use in solid formulation. US 2011/0065746A1. Patent published on 17^th March 2011.

24.   Ananda Kumar.CH. et al Development, formulation and evaluation of Solifenacin Succinate immediate release oral tablets by using starch and hpmc. International Journal of Research in Pharmaceutical and Nano sciences. 2013; 2(1): 91-100.

25. Suh Young Hee. et al Stable composition comprising Solifenacin. WO 2015/115750 A1. Patent published on 6^th August 2015.

26.   Naga Sudha. RKV. et al Design, Development and Evaluation of Solifenacin Succinate Tablets. Research Journal of Pharmaceutical Dosage Forms and Technology. 2015; 7(2): 111-117. doi: 10.5958/0975-4377.2015.00016.6

27. Hari Prasad Bhatta. et al Formulation and evaluation of Solifenacin Succinate immediate release tablets using various superdisintegrants. World Journal of Pharmacy and Pharmaceutical Sciences. 2016; 5(6): 768-781. DOI: 10.20959/wjpps20166-6633

28. Bhavana V. et al RP-HPLC method for estimation of Solifenacin Succinate in API and Tablet dosage form. Asian Journal of Pharmaceutical Analysis. 2019;9(3):118-122. DOI:10.5958/2231-5675.2019.00022.X

29. Rihana Parveen Shaik. et al Analytical method development and validation of Solifenacin in pharmaceutical dosage forms by RPLC. ISRN Analytical Chemistry. 2014;4(3):1-5. DOI: 10.1155/2014/132020

30. Lokesh Singh. et al Spectrophotometric estimation of Solifenacin Succinate in tablet formulations. Pharmaceutical Methods. 2011;2(1):21-24. Doi: 10.4103/2229-4708.81086.

31. Vijayasree V. et al Validated RP-HPLC Method For The Estimation of Solifenacin Succinate In Tablet Dosage Forms. Pharmanest. 2013; 4(2): 206-212.

32. Radhakrishna S. et al A validated rapid stability-indicating method for the determination of related substances in Solifenacin Succinate by ultra-fast liquid chromatography. Journal of Chromatographic Science. 2010;48(10):807-810. Doi: 10.1093/chromsci/48.10.807.

33. Shashikant B Landge. et al Development and validation of new chromatographic method for the determination of enatiomeric and diastereomeric purity of Solifenacin Succinate: An Antimuscarinic Agent. Chromatography Research International. 2011; 7(7): 7 pages. Doi:10.4061/2011/243491.

34. Nilesh Desai. et al Development and validation of stability indicating HPLC method for determination of Solifenacin in bulk formulations. 2011;3(1):70-74.

35. Divya Teja G. et al Quantitative analysis of Solifenacin Succinate in pharmaceutical dosage form using UV absorption spectroscopy. 2013;6(3):195-198.

36. Rakesh B. et al UV Spectrophotometric method development and validation for the quantitative estimation of Solifenacin Succinate in Tablets. International Journal of Pharmacy and Pharmaceutical Sciences. 2014;6(10):190-193.

37. Seetharaman R. et al Development and validation of first order derivative spectrophotometric method for estimation of Solifenacin Succinate in pharmaceutical formulation. International Journal of Research in Pharmaceutical and Biomedical Sciences. 2011; 2(3): 1052-1057.

38. Saroj Kumar R. et al A RP-HPLC method development and validation for the estimation of Solifenacin in bulk and pharmaceutical dosage forms. International Journal of Bioassays. 2012;01(12):210-213.

39. Mathrusri Annapurna M. et al A validated liquid chromatographic method for the determination of Solifenacin Succinate (Urinary Antispasmodic) in Tablets. Chemical Science Transactions. 2014;3(2):602-607.

40. Desai D. et al Development and validation of stability-indicating HPLC method for Solifenacin Succinate: Isolation and identification of major degradation product. Acta Chromatographica. 2012;24(3):399-418. DOI: https://doi.org/10.1556/achrom.24.2012.3.5.

41. Rami Reddy BV. et al Development and validation of specific stability indicating high performance liquid chromatographic methods for related compounds and assay of Solifenacin Succinate. Journal of Chemistry. 2013;1-10. DOI: https://doi.org/10.1155/2013/412353.

42. Madhu Kiran M. et al Two direct simple visible spectrophotometric assay methods of Solifenacin Succinate in oral tablet formulations. Resayan Journal of Chemistry. 2017;10(4): 1068-1074.

43. General chapters in USP Pharmacopoeia related to Disintegration, Friability, Repose Angle, Compressibility Index, Hausner Ratio etc.

44. https://www.colorcon.com/products-formulation/all-products/film-coatings/immediate-release/opadry-ii/item/75-opadry-ii-coating.

45. https://www.perrigo.com.au/upload/product/document/ORA03317F_PB.pdf.

46. https://clinicaltrials.gov/ct2/show/NCT01015040.

47. https://www.fda.gov/media/148472/download

Received on 16.06.2021 Modified on 20.08.2021

Research J. Pharm. and Tech 2022; 15(9):4166-4172.

DOI: 10.52711/0974-360X.2022.00699

Particulars	VESICARE^® 5 mg	VESICARE^® 10 mg
Description	Light yellow colored round tablet debossed with logo and 150 on one side and plain on the other side	Light pink colored round tablet debossed with logo and 150 on one side and plain on the other side
Count	30 tablets	90 tablets
Diameter, mm	7.61 – 7.63	7.62-7.63
Weight, mg	151-155	152-157
Thickness, mm	3.48-3.50	3.46-3.51
Hardness, kP	4.6-5.6	6.5-6.7
Disintegration time, min	9-9.1	10-10.2
% Average Dissolution in 15 min using USP-II (Paddle), 50 RPM, 900 mL, Purified Water	89-95%	87-93%
pH (1% slurry)	4.97	4.73
Loss on drying (105^°C / Automode)	4.83	4.06
Assay (%)	99.5	99.3
Highest Unknown Impurity (%) Total Impurity (%)	0.02 0.11	0.03 0.13
Excipients	Lactose Monohydrate, Corn Starch, Hypromellose 2910, Magnesium Stearate, Talc, Polyethylene Glycol 8000, Titanium dioxide with yellow ferric oxide or red ferric oxide
Pack	High density polyethylene bottle with polypropylene Child resistant closure
Storage	Store at 25^°C (77^°F) excursions permitted to 15^°C-30^°C (59^°F-86^°F). See USP controlled room temperature
Manufactured by	Astellas Pharm US, Inc

Particulars	VESICARELS™
Label Claim	An oral suspension containing 1mg/mL of Solifenacin Succinate equivalent to 0.75mg/mL of Solifenacin
Description	White to off-white colored suspension
pH	5.4 - 7
Viscosity	300 – 400 cps
Assay	99.5%
Highest Unknown Impurity (%) Total Impurity (%)	0.05 0.14
Microbial Load	Absent
Organoleptics	Palatable
% Average Dissolution	99% in 15 min using USP-II (Paddle), 50 RPM, 900mL, Purified Water
Excipients	Polacrilin Potassium, Methyl Paraben, Propyl Paraben, Propylene Glycol, Simethicone Emulsion 30%, Carbomer homopolymer Type B, Xylitol, Acesulfame Potassium, Natural Orange Flavour, Sodium Hydroxide and Purified Water.
Pack	150mL amber polyethylene terephthalate (PET) bottles, which are capped with child-resistant high-density polyethylene-polypropylene caps with a pulp and vinyl seal liner.
Storage	Store at 20°C to 25°C (68°F to 77°F) with excursions permitted from 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Store in original bottle to protect from degradation. Dispense in a tight, light-resistant container. Discard any unused product 28 days after opening the original bottle.
Manufactured by	Astellas Pharm US, Inc