Sustained release matrix tablet of 100 mg losartan potassium: Formulation development and <i>in vitro</i> characterization

Devi, Diksha; Ghosh, Animesh; Mandal, Uttam Kumar

doi:10.1590/s2175-97902022e20079

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Brazilian Journal of Pharmaceutical Sciences

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Article • Braz. J. Pharm. Sci. 58 • 2022 • https://doi.org/10.1590/s2175-97902022e20079 copy

Sustained release matrix tablet of 100 mg losartan potassium: Formulation development and in vitro characterization

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Sustained release matrix tablets of 100 mg losartan potassium HCl were fabricated with two release retarding polymers namely HPMC K100 M and affinisol by direct compression method. Nine trial formulations were prepared by varying content of these polymers, each from 50 mg to 100 mg; keeping the total weight of the tablet 310 mg. The best formulation was selected based on in vitro drug release profile for 12 hours conducted in Type II dissolution apparatus at 50 rpm and water as dissolution medium. Pre-compression parameters such as bulk density, tap density, Carr’s index and Hausner ratio were evaluated for the selected tablet. The tablets were subjected to thickness, weight variation test, drug content, hardness and friability. Drug release kinetics, surface morphology and accelerated stability study were investigated for that selected formulation. Formulation F4 with the composition of 75 mg HPMC K100M and 100 mg affinisol was selected as the best formulation that extended the drug release up to 12 hours. Pre-compression parameters and other tableting properties were within the Pharmacopoeia limit. Release kinetics analysis proved non-fickian zero-order drug release and that was further confirmed by surface morphology of the tablets before and after dissolution study visualized by SEM. The developed formulation was found to be stable for one month stored at 60 ^○C.

Keywords:
Hypertension; Losartan potassium; Sustained-release matrix tablet; HPMC; Affinisol; Formulation development

Sr. No	Ingredients	Trial formulations (each composition in mg)
Sr. No	Ingredients	F1	F2	F3	F4	F5	F6	F7	F8	F9
1	HPMC K100M	100	100	100	75	75	75	50	50	50
2	Affinisol	100	75	50	100	75	50	100	75	50
3	Losartan potassium	100	100	100	100	100	100	100	100	100
4	Talc	3	3	3	3	3	3	3	3	3
5	Magnesium stearate	3	3	3	3	3	3	3	3	3
6	Lactose	4	29	54	29	54	79	54	79	104
7	Total weight (mg)	310	310	310	310	310	310	310	310	310

Time (hours)	F1	F2	F3	F4	F5	F6	F7	F8	F9
0	0.00	0.00	0.00	0.00	0.00	0.00	0.00	0.00	0.00
0.5	16.98 ± 2.21	17.65 ± 1.60	19.41 ± 1.55	12.59 ± 1.18	14.31 ± 4.16	16.10 ± 2.53	17.17 ± 3.52	21.34 ± 2.53	22.82 ± 1.27
1	19.85 ± 2.02	21.85 ± 1.96	23.25 ± 0.75	15.90 ± 1.11	17.46 ± 2.92	28.66 ±3.06	30.12 ± 1.08	31.71 ± 1.65	32.60 ± 2.65
1.5	24.08 ± 2.45	26.87 ± 2.67	28.55 ± 2.81	19.28 ± 1.61	23.38 ± 2.13	36.79 ± 3.75	37.87 ± 1.46	40.01 ± 5.13	41.60 ± 1.52
2	29.22 ± 3.74	32.96 ± 3.34	35.11 ± 4.64	28.97 ± 2.54	32.50 ± 2.48	41.95 ± 4.09	42.45 ± 1.11	44.34 ± 3.88	46.22 ± 2.58
3	37.30 ± 3.91	48.42 ± 0.99	49.56 ± 1.07	37.34 ± 5.27	40.67 ± 2.98	50.37 ± 3.58	51.72 ± 0.90	53.05 ± 3.98	56.53 ± 4.92
4	44.15 ± 2.46	53.10 ± 1.48	57.08 ± 1.06	47.30 ± 9.38	49.38 ± 2.09	62.66 ± 5.05	61.37 ± 2.02	63.97 ± 2.33	65.94 ± 7.22
5	52.61 ± 1.79	63.14 ± 1.43	65.91 ± 3.69	53.97 ± 7.59	55.48 ± 1.91	69.28 ± 4.73	68.11 ± 1.79	72.85 ± 4.46	73.74 ± 3.79
6	61.35 ± 1.55	69.45 ± 1.52	73.01 ± 5.49	60.47 ± 4.10	65.17 ± 2.22	78.17 ± 4.33	78.69 ± 1.90	79.08 ± 3.75	81.98 ± 4.32
8	71.45 ± 2.85	75.51 ± 2.64	77.60 ± 6.13	74.30 ± 3.58	77.36 ± 3.12	90.04 ± 3.56	92.59 ± 3.77	93.27 ± 3.27	95.01 ± 3.45
10	82.82 ± 3.04	85.64 ± 3.06	87.21 ± 6.38	86.18 ± 4.97	90.93 ± 3.55	97.47 ± 2.84	98.32 ± 4.21	98.75 ± 2.33	101.15 ± 4.56
12	89.85 ± 3.55	93.89 ± 3.92	95.12 ± 7.05	99.70 ± 4.01	101.14 ± 4.22	100.58 ± 3.24	102.93 ± 3.34	101.76 ± 2.54	100.10 ± 4.72

Bulk Density	Tapped Density	Hausner’s Ratio	Carr’s Index	Angle of Repose
0.414gm/cc	0.469gm/cc	1.13	11.72	26.5°

Weight variation	Thickness (±SD)	Diameter (±SD)	Friability	Hardness (±SD)	Drug Content (±SD)
0.37 ±0.04%	4.45 ± 0.02 mm	9.93 ±0.01 mm	0.48%	8.87 ± 0.95 Kg/cm²	97.80 ± 0.57%

Model	Parameters
Zero order	K₀ = 7.9366 , R² = 0.9892
First order	K₁ = 0.3488, R² = 0.8512
Higuchi	K_H = 29.7670 , R² = 0.9879
Korsmeyer Peppas	K_KP = 0.1749, n =0.692 , R² =0.9860

Time	R_t	T_t	(R_t-T_t)	(R_t-T_t)²
30	12.59	6.95	5.64	31.8096
60	15.9	14.73	1.17	1.3689
90	19.28	19.09	0.19	0.0361
120	28.97	22.74	6.23	38.8129
240	47.3	38.04	9.26	85.7476
360	60.47	53.58	6.89	47.4721
480	74.3	64.89	9.41	88.5481
600	86.18	86.86	0.68	0.4624
		sum (R_t-T_t)		39.47
		sum (R_t-T_t)²		294.2577
sum Rt				344.99
		Similarity factor f2		53
		Difference factor f1		11

Universidade de São Paulo, Faculdade de Ciências Farmacêuticas Av. Prof. Lineu Prestes, n. 580, 05508-000 S. Paulo/SP Brasil, Tel.: (55 11) 3091-3824 - São Paulo - SP - Brazil
E-mail: bjps@usp.br

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[1] *Correspondence: U. K. Mandal. Department of Pharmaceutical Sciences & Technology. Maharaja Ranjit Singh Punjab Technical University (MRSPTU). Badal Road, Bathinda, Punjab-151001, India. Hand Phone: +91 9872419542. E-mail: mandalju2007@gmail.com.