Development and optimization of metoclopramide containing polymeric patches: impact of permeation enhancers

Sarwar, Zunaira; Farooq, Muhammad; Adnan, Sherjeel; Saleem, Muhammad Umer; Masood, Zeeshan; Mahmood, Asif

doi:10.1590/s2175-97902022e21131

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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/s2175-97902022e21131 copy

Development and optimization of metoclopramide containing polymeric patches: impact of permeation enhancers

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

The study is aimed to develop a monolithic controlled matrix transdermal patches containing Metoclopramide as a model drug by solvent casting method. Eudragit L100, Polyvinylpyrrolidone K-30, and Methylcellulose were used in different ratios and Polyethylene glycol 400 added as a plasticizer. Resulting patches were evaluated for their physicochemical characters like organoleptic characters, weight variation, folding endurance, thickness, swelling index, flatness, drug content, swelling index, percentage erosion, moisture content, water vapor transmission rate and moisture uptake. Formed patches were also evaluated through Fourier transform spectroscopy (FT-IR), X-ray diffraction (XRD), Differential Scanning calorimetry (DSC) and Scanning Electron Microscopy (SEM). Results of SEM unveiled smooth surface of drug-loaded patches. In-vitro dissolution studies were conducted by using dissolution medium phosphate buffer saline pH 7.4. Effect of natural permeation enhancers was elucidated on two optimized formulations (Z4 and Z9). Different concentrations (5%-10 %) of permeation enhancers i.e. Olive oil, Castor oil and Eucalyptus oil were evaluated on Franz diffusion cell using excised abdominal rat skin. Z4-O2 (Olive oil 10%) had enhanced sustain effect and flux value (310.72) close to the desired flux value. Z4-O2 followed Higuchi release model (R²= 0.9833) with non-fickian diffusion release mechanism (n=0.612).

Keywords:
Matrix transdermal patch; Metoclopramide; Eudragit L100; Essential oil; Permeation enhancer; Flux

Formulation	Eudragit L-100 (mg)	PVP K-30 (mg)	Methylcellulose (mg)	Chloroform : Methanol (ml)	Permeation enhancer
Z1	500	-	-	5:5	-
Z2	400	100	-	5:5	-
Z3	300	200	-	5:5	-
Z4	200	300	-	5:5	-
Z5	100	400	-	5:5	-
Z6	-	500	-	5:5	-
Z7	400	-	100	0:10	-
Z8	300	-	200	0:10	-
Z9	200	-	300	0:10	-
Z10	100	-	400	0:10	-
Z11	-	-	500	0:10	-
Z4-O1	200	300	-	5:5	Olive oil (5%)
Z4-O2	200	300	-	5:5	Olive oil (10%)
Z4-C1	200	300	-	5:5	Castor oil (5%)
Z4-C2	200	300	-	5:5	Castor oil (10%)
Z4-E1	200	300	-	5:5	Eucalyptus oil (5%)
Z4-E2	200	300	-	5:5	Eucalyptus oil (10%)
Z9-O1	200	-	300	0:10	Olive oil (5%)
Z9-O2	200	-	300	0:10	Olive oil (10%)
Z9-C1	200	-	300	0:10	Castor oil (5%)
Z9-C2	200	-	300	0:10	Castor oil (10%)
Z9-E1	200	-	300	0:10	Eucalyptus oil (5%)
Z9-E2	200	-	300	0:10	Eucalyptus oil (10%)

Formulation	Weight variation ± S.D. (mg)	Thickness ± S.D. (mm)	Folding endurance	Flatness ± S.D. (%)	Moisture uptake (%)
Z1	1.2683 ± 0.0268	0.050279 ± 2.83 x 10^-5	˂100	100 ± 0	2.12
Z2	1.2360 ± 0.0102	0.050262 ± 2.20 x 10^-5	˂100	100 ± 0	4.86
Z3	1.2372 ± 0.0231	0.050271 ± 2.68 x 10^-5	˂100	100 ± 0	8.40
Z4	1.2241± 0.0101	0.050375 ± 8.79 x 10^-5	˂100	99.54 ± 0.48	11.70
Z5	1.2436 ± 0.0329	0.050498 ± 7.35 x 10^-5	˂100	98.64 ± 0.50	13.21
Z6	1.2192 ± 0.0204	0.050454 ± 3.51 x 10^-5	˃150	97.39 ± 0.35	19.31
Z7	1.2041± 0.0190	0.050357 ± 1.33 x 10^-5	˂100	100 ± 0	7.46
Z8	1.2426 ± 0.0140	0.050387 ± 1.50 x 10^-5	˂100	100 ± 0	8.91
Z9	1.2180 ± 0.0102	0.050372 ± 5.10 x 10^-5	˂100	100 ± 0	13.41
Z10	1.2390 ± 0.0074	0.05034 ± 1.60 x 10^-5	˂100	100 ± 0	15.18
Z11	1.2256 ± 0.0175	0.050447 ± 2.08 x 10^-5	˃150	97 ± 0	10.63

Formulation	Swelling Index ± (SD)	Percentage Erosion (%)	WVTR (g/m2.hr)	Drug content (%) ± S.D.
Z1	0.92 ± 0.0250	4.71 ± 0.212	9.54 x 10^-4	99.79 ± 0.017
Z2	1.24 ± 0.0458	8.42 ± 0.233	21.4 x 10^-4	99.28 ± 0.026
Z3	1.52 ± 0.0741	13.06 ± 0.274	19.2 x 10^-4	98.46 ± 0.032
Z4	1.85 ± 0.0854	17.71 ± 0.698	15.8 x 10^-4	100.38 ± 0.01
Z5	Disintegrated after 10 min		10.25 x 10^-4	100.12 ± 0.02
Z6	Disintegrated after 10 min		24.14 x 10^-4	99.97 ± 0.029
Z7	1.07 ± 0.0478	9.03 ± 0.306	19.5 x 10^-4	98.83 ± 0.043
Z8	1.12 ± 0.0358	10.97 ± 0.549	18.5 x 10^-4	98.30 ± 0.045
Z9	1.22 ± 0.0650	16.27 ± 0.404	15.6 x 10^-4	98.80 ± 0.062
Z10	1.56 ± 0.0414	24.19 ± 0.763	24.4 x 10^-4	100.22 ± 0.02
Z11	Disintegrated after 10 min		12.6 x 10^-4	98.31 ± 0.035

Formulation	Zero order	First order	Higuchi	Krosmeyer-Peppas		Weibull
Formulation	R2	R2	R2	R2	n	R2	β
Z1	0.9921	0.9818	0.8931	0.9947	0.917	0.9920	1.030
Z2	0.9944	0.9822	0.8807	0.9980	0.699	0.9988	0.814
Z3	0.9893	0.9825	0.9397	0.9912	0.751	0.9889	0.875
Z4	0.9914	0.9799	0.8761	0.9919	0.964	0.9857	1.149
Z5	0.9837	0.9690	0.9914	0.9981	0.825	0.9991	1.010
Z6	0.9974	0.9877	0.8886	0.9990	0.935	0.9966	1.186
Z7	0.8544	0.9255	0.9846	0.9921	0.577	0.9935	0.673
Z8	0.8569	0.9261	0.9791	0.9874	0.583	0.9880	0.682
Z9	0.6444	0.8105	0.9710	0.9757	0.449	0.9823	0.554
Z10	0.6196	0.7946	0.9615	0.9693	0.435	0.9743	0.544
Z11	0.9601	0.9525	0.9240	0.9862	0.777	0.9900	1.524

Formulation	Slope	Flux (μg/cm²hr)	Permeability coefficient (cm/hr)	Extraction ratio (ER)
Z4	151.17	125.98	0.0151	-
Z9	173.39	144.49	0.0173	-
Z4-O1	241.97	201.64	0.0241	1.60
Z4-O2	372.87	310.72	0.0372	2.46
Z4-C1	328.35	273.62	0.0328	2.17
Z4-C2	343.55	286.29	0.0343	2.27
Z4-E1	298.30	248.59	0.0314	1.97
Z4-E2	358.46	298.71	0.0362	2.37
Z9-O1	219.74	183.11	0.0219	1.26
Z9-O2	280.54	233.78	0.0280	1.62
Z9-C1	241.85	201.54	0.0241	1.40
Z9-C2	293.70	244.75	0.0293	1.71
Z9-E1	273.75	228.13	0.0298	1.57
Z9-E2	343.24	286.03	0.0369	1.97

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: M. Farooq. Faculty of Pharmacy. The University of Lahore. Lahore, Pakistan. Phone: +923346901320. E-mail: muhammad.farooq@pharm.uol.edu.pk.