An overview of preparation and characterization of solid binary system and its application on transdermal film with variation of plasticizers

Kahali, Nancy; Khanam, Jasmina; Chatterjee, Himadrija

doi:10.1590/s2175-97902022e191123

Nancy Kahali ^**Correspondence: N. Kahali. Department of Pharmaceutical Technology. Jadavpur University. India. Phone: +918013613230. kahalinancy@gmail.com jasminakhanam@gmail.com himadrijabuiya@gmail.com

Department of Pharmaceutical Technology, Jadavpur University, India

http://orcid.org/0000-0002-9878-4792

Jasmina Khanam

Department of Pharmaceutical Technology, Jadavpur University, India

Himadrija Chatterjee

Department of Pharmaceutical Technology, Jadavpur University, India

*Correspondence: N. Kahali. Department of Pharmaceutical Technology. Jadavpur University. India. Phone: +918013613230. kahalinancy@gmail.com jasminakhanam@gmail.com himadrijabuiya@gmail.com

CONFLICT OF INTEREST

The authors declare no conflicts of interest.

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FIGURE 1
Phase solubility analysis of a) HPβCD-OND at DDW; b) HPβCD-OND at pH 7.4; c) PVP K-30-OND at DDW; d) PVP K-30-OND at pH 7.4; e) HPβCD-OND at pH 6.8; f) HPβCD-OND at pH 6.8 at different temperatures.

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FIGURE 2
Aqueous solubility of OND in different pH at 25 and 37˚C.

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FIGURE 3
In-vitro diffusion profile of a) Pure OND loaded patches b) SD loaded patches.

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FIGURE 4
Ex-vivo permeation profile of a) Pure drug loaded patch b) SD loaded patches.

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FIGURE 5.1
FTIR spectra of a) OND HCl, b) OND c) EC d) PVP K-30e) HPβCDf) HPMC.

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FIGURE 5.2
FTIR spectra of a) OND-HPβCD 1:1 binary complex; b) OND-HPβCD 1:3 binary complex; c) OND-HPβCD 1:5 binary complex d) OND-PVP K-30 1:1 binary complex; e) OND-PVP K-30 1:3 binary complex; f) OND-PVP K-30 1:5 binary complex.

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FIGURE 5.3
FTIR spectra of I) 30% PEG with pure drug loaded patch; II) 40% PEG with pure drug loaded patch; III) 30% DBP with pure drug loaded patch; IV) 40% DBP with pure drug loaded patch; V) 50% DBP with pure drug loaded patch, VI) 30% PEG with SD loaded patch; VII) 40% PEG with SD loaded patch; VIII) 30% DBP with SD loaded patch; IX) 40% DBP with pure drug loaded patch; X) 50% DBP with pure drug loaded patch.

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FIGURE 6
DSC thermogram ofa)OND HCl; b)OND.

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FIGURE 6.1
Differential scanning calorimetry study of a) OND-PVP K-30 1:1 w/w SD; b) OND-PVP K-30 1:3 w/w SD; c) OND-PVP K-30 1:5 w/w SD; d) OND-HPβCD 1:1 w/w SD; e) OND-HPβCD 1:3 w/w SD; f) OND-HPβCD 1:5 w/w SD.

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FIGURE 7
Scanning electron micrographs of a) OND-PVP K-30 1:5 w/w SD; b) blank patch; c) pure drug loaded patch with 40% PEG; d) pure drug loaded patch with 50% DBP; e) SD loaded patch with 40% PEG; f) SD loaded patch with 50% DBP.

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TABLE I
Batch of formulations

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TABLE II
Study of Partition coefficient

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TABLE III
Thermodynamic parameters for the reciprocation of Ondansetron with PVP K30 and HPβCD

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TABLE IV
Solubility study of OND and OND-SD

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TABLE V
Data of Percentage moisture content, percentage moisture absorption and percentage drug content. (n=3)

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TABLE VI
Thickness, adhesion property and content uniformity of different patches (n=3)

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TABLE VII
Tack properties of different patches (n=3)

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TABLE VIII
Permeation parameters of different formulations (n=3)

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TABLE IX
Kinetic study of pure OND and SD loaded patches

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(1)

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(2)

Patch code	Carriers				Total weight of carriers (mg)	Chloroform (mL)	% DBP (total wt. of polymer)	% PEG(total wt. of polymer)	Drug (mg)
Patch code	PVP K30 (mg)	HPMC (mg)	EC (mg)	SD (1:5w/w OND-PVP K-30)	Total weight of carriers (mg)	Chloroform (mL)	% DBP (total wt. of polymer)	% PEG(total wt. of polymer)	Drug (mg)
P1	50	5	10	-	65	3	30% v/w	30% v/w	10
P2	50	5	10	-	65	3	40% v/w	40% v/w	10
P3	50	5	10	-	65	3	50% v/w	50% v/w	10
P4*	-	-	-	78	-	3	30% v/w	30% v/w	10
P5*	-	-	-	78	-	3	40% v/w	40% v/w	10
P6*	-	-	-	78	-	3	50% v/w	50% v/w	10

Formulations	Log P value in octanol-water	Log P value in octanol- pH 7.4 buffer
OND HCl	2.43±0.002	2.36±0.003
OND	2.52±0.005	2.45±0.01
*OND: HPβCD(1:1 w/w)	2.58±0.01	2.49±0.001
*OND: HPβCD(1:3 w/w)	2.64±0.002	2.54±0.004
*OND: HPβCD(1:5 w/w)	2.73±0.005	2.59±0.005
*OND: PVP K-30 (1:1 w/w)	2.52±0.004	2.60±0.002
*OND: PVP K-30(1:3 w/w)	2.61±0.002	2.66±0.001
*OND: PVP K-30(1:5 w/w)	2.85±0.01	2.78±0.001

Carrier	Temperature in ˚C	Temperature in K	DDW (kJ/Mole)		pH 7.4 (kJ/Mole)		pH 6.8 (kJ/Mole)
Carrier	Temperature in ˚C	Temperature in K	^* K _a , M ^-1	(∆G, ∆H, *∆S)	K_a, M^-1	(∆G, ∆H, ∆S)	K_a, M^-1	(∆G, ∆H, ∆S)
PVP K30	25	303	7160.9	∆G = -22.36	3157.16	∆G = -20.29	1156.77	∆G = -17.76
				∆H = 4.42		∆H = 60.82		∆H = 27.37
				∆S = 0.088		∆S = 0.267		∆S = 0.148
	37	310	7450.53	∆G = -22.97	5446.01	∆G = -22.17	1478.41	∆G = -18.81
				∆H = 13.32		∆H = 79.14		∆H = 65.52
				∆S = 0.11		∆S = 0.326		∆S = 0.272
	40	313	7829.13	∆G = -23.33	7309.83	∆G = -23.15	1886.39	∆G = -19.62
				∆H =1.77		∆H = 84.82		∆H = 74.02
				∆S = 0.08		∆S = 0.344		∆S = 0.299
	45	318	7913.6	∆G = -23.73	12203.6	∆G = -24.87	2950.37	∆G = -21.12
HPβCD	25	303	54.43	∆G = -10.06	158.66	∆G = -12.76	58.21	∆G = -10.23
				∆H = 20.62		∆H = 10.05		∆H = 3.95
				∆S = 0.10		∆S = 0.075		∆S = 0.046
	37	310	65.49	∆G = -10.77	173.62	∆G = -13.29	60.31	∆G = -10.56
				∆H = 19.77		∆H = 12.39		∆H = 4.60
				∆S = 0.098		∆S = 0.082		∆S = -0.008
	40	313	70.49	∆G = -11.07	181.81	∆G = -13.53	61.35	∆G = -10.71
				∆H = 34.65		∆H = 5.16		∆H = 6.09
				∆S = 0.146		∆S = 0.059		∆S = 0.053
	45	318	86.91	∆G = -11.80	187.57	∆G = -13.83	63.65	∆G = -10.98

Carrier-Drug Ratio (w/w)	Temperature (ºC)	Solubility in DDW (µg/mL)	Solubility at pH 6.8 (µg/mL)	Solubility at pH 7.4 (µg/mL)
PURE OND	25	187±0.03	451.23±0.03	188.48±0.02
PURE OND	37	253.10±0.0	512.96±0.04	216.36±0.02
OND:HPβCD (1:1 w/w)	25	251.41±0.02	578.39±0.01	285.45±0.005
OND:HPβCD (1:1 w/w)	37	403.38±0.004	711.72±0.04	298.18±0.04
OND:HPβCD (1:3 w/w)	25	443.50±0.02	712.34±0.02	578.18±0.05
OND:HPβCD (1:3 w/w)	37	543.50±0.06	858.02±0.002	561.81±0.03
OND:HPβCD (1:5 w/w)	25	712.99±0.03	824.69±0.006	850.30±0.01
OND:HPβCD (1:5 w/w)	37	844.06±0.01	956.17±0.03	872.72±0.06
OND:PVP K-30 (1:1 w/w)	25	388.13±0.05	582.09±0.004	334.54±0.008
OND:PVP K-30 (1:1 w/w)	37	588.70±0.01	722.83±0.006	390.90±0.002
OND:PVP K-30 (1:3 w/w)	25	702.25±0.01	720.98±0.004	558.18±0.02
OND:PVP K-30 (1:3 w/w)	37	776.83±0.06	861.11±0.03	687.87±0.001
OND:PVP K-30 (1:5 w/w)	25	889.26±0.04	954.93±0.01	863.03±0.002
OND:PVP K-30 (1:5 w/w)	37	894.91±0.009	990.74±0.01	972.72±0.003

Patch code	% MC		% MA		% DC
Patch code	PEG	DBP	PEG	DBP	PEG	DBP
P1	1.29±0.06	1.11±0.032	3.14±0.2	1.28±0.71	91.39±1.04	94.53±0.02
P2	1.28±0.045	1.21±0.051	3.37±0.31	1.92±0.32	92.18±1.81	96.91±2.36
P3	1.31±0.02	1.06±0.035	1.97±0.15	1.01±0.2	87.45±1.81	93.76±4.92
P4*	2.77±0.047	1.89±0.043	3.64±0.04	1.90±0.023	92.18±3.14	96.12±2.09
P5*	3.10±0.023	2.22±0.031	3.83±0.052	2.62±0.02	94.54±1.81	95.33±1.04
P6*	2.41±0.04	1.23±0.012	2.79±0.046	2.10±0.031	92.18±3.63	95.33±3.78

Patch code	Thickness (mm)		Adhesion property		Drug content uniformity (%)
Patch code	PEG	DBP	PEG	DBP	PEG	DBP
P1	0.086±0.009	0.084±0.006	+++	+++	89.03±2.7	91.38±5.9
P2	0.089±0.004	0.086±0.0025	+++	+++	90.60±3.7	94.54±2.36
P3	0.089±0.003	0.084±0.005	+	++	86.67±2.7	92.18±2.36
P4*	0.086±0.002	0.089±0.008	+++	+++	88.24±4.5	95.33±2.7
P5*	0.085±0.004	0.088±0.003	+++	+++	91.39±3.78	93.76±3.78
P6*	0.085±0.004	0.089±0.003	+	+++	89.03±2.0	92.97±2.7

Patch code	Adhesive properties (g/cm²)		Work of adhesion (g.s)		Average separation distance (mm)
Patch code	PEG	DBP	PEG	DBP	PEG	DBP
P1	1216.76±149.54	1104±176.49	32.49±9.12	33.89±10.30	1.33±0.52	1.26±0.5
P2	1019.12±124.78	1156±216.06	35.72±7.39	36.46±9.16	1.20±0.70	1.34±0.63
P3	1072.84±163.46	1095.40±115.94	27.39±7.11	38.73±10.59	1.67±0.27	1.38±0.6
P4*	1227.38±182.60	1279±208.77	39.24.±10.21	33.23±8.66	1.34±0.5	1.10±0.12
P5*	1165.89±204.19	1180±136.72	34.12±9.48	35.69±8.45	1.29±0.5	1.22±0.18
P6*	1110.34±146.44	1294.85±221.09	39.52±10.31	40.91±9.88	1.23±0.35	1.18±0.21

Formulation code	R² value		Flux, Jss (μg/cm²/h)		Kp (cm/h)		Enhancement factor of flux (Jss)
PURE OND	0.984		0.80±0.14		0.24±0.2		-
Plasticizers	PEG	DBP	PEG	DBP	PEG	DBP	PEG	DBP
P1	0.987±0.004	0.979±0.006	5.02±0.59	5.48±0.48	0.164±0.02	1.47±1.22	6.27	6.85
P2	0.975±0.01	0.963±0.01	5.51±1.87	5.57±0.057	0.151±0.04	0.221±0.025	6.88	6.96
P3	-	0.985±0.004	-	6.23±0.59	-	0.541±0.17	-	7.78
P4*	0.921±0.02	0.982±0.007	5.63±0.77	5.68±0.45	0.097±0.02	1.64±1.20	7.03	7.10
P5*	0.942±0.006	0.958±0.01	6.74±0.23	6.44±0.22	0.106±0.011	0.20±0.06	8.42	8.05
P6*	-	0.959±0.01	-	6.64±0.18	-	0.12±0.02	-	8.30

Patch code	Models	Coefficient of determination (R²)		Release Mechanism
Patch code	Models	DBP	PEG	DBP	PEG
P1	Higuchi	0.976	0.973
	Zero order	0.991	0.989	First order	First order
	First order	0.993	0.990
P2	Higuchi	0.988	0.989
	Zero order	0.980	0.980	First order	First order
	First order	0.991	0.992
P3	Higuchi	0.990	-
	Zero order	0.989	-	Higuchi	-
	First order	0.984	-
P4*	Higuchi	0.991	0.990
	Zero order	0.990	0.925	Higuchi	Higuchi
	First order	0.990	0.983
P5*	Higuchi	0.992	0.991
	Zero order	0.970	0.944	Higuchi	Higuchi
	First order	0.985	0.956
P6*	Higuchi	0.990	-
	Zero order	0.962	-	Higuchi	-
	First order	0.976	-

[1] *Correspondence: N. Kahali. Department of Pharmaceutical Technology. Jadavpur University. India. Phone: +918013613230. kahalinancy@gmail.com jasminakhanam@gmail.com himadrijabuiya@gmail.com

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An overview of preparation and characterization of solid binary system and its application on transdermal film with variation of plasticizers

Abstract