The objective of this study was to investigate the mechanism of release of econazole nitrate (EN) nanosponges loaded hydrogel and to compare it with EN hydrogel so as to develop an extended release topical drug delivery system of EN. Nanosponges of EN were prepared using ethyl cellulose and PVA by emulsion solvent evaporation method. On the basis of pharmacotechnical evaluation nanosponges with least particle size of 230.1 nm and good rheological properties were formulated as hydrogel (F1 – F7). In vitro drug release data of EN nanosponges loaded hydrogels in phosphate buffer pH 6.8 and 7.4 when analysed by GraphPad Prism software version 4.0 San Diego, USA best fitted the Makoid-2 Banakar model (R value greater than 0.98). The Korsmeyer-Peppas release exponent (n) ranged between 0.331 – 0.418, which confirmed diffusion as the principle mechanism of drug release. The release mechanism was further confirmed by calculating the ratio of exponents A/B ratio derived from the Kopcha model

Pathak, K

Sharma, R

Walker, Roderick

Sharma, R.

Walker, R.B.

Pathak, K.

SEALS Digital commons

Evaluation of the kinetics and mechanism of drug release from Econazole nitrate nanosponge loaded Carbapol Hydrogel.

Sharma, Renuka

Walker, Roderick B

Pathak, Kamla

Rhodes Repository (SEALS)

Indian Journal of Pharmaceutical Education and  Research Association  of Pharmaceutical Teachers of IndiaEvaluation of the Kinetics and Mechanism of Drug Release from Econazole nitrate Nanosponge Loaded Carbapol Hydrogel1 2 1Renuka Sharma , Roderick B. Walker  and Kamla Pathak *1Rajiv Academy for Pharmacy, National Highway #2, P.O. Chhattikara, Mathura, Uttar Pradesh (INDIA) 2810012Faculty of Pharmacy, Rhodes University, Grahamstown, South Africa 6140A B S T R A C TThe objective of this study was to investigate the mechanism of release of econazole nitrate (EN) nanosponges loaded hydrogel and to compare it with EN hydrogel so as to develop an extended release topical drug delivery system of EN. Nanosponges of EN were prepared using ethyl cellulose and PVA by emulsion solvent evaporation method. On the basis of pharmacotechnical evaluation nanosponges with least particle size of 230.1 nm and good rheological properties were formulated as hydrogel (F1 – F7).  In vitro drug release data of EN nanosponges loaded hydrogels  in phosphate buffer pH 6.8 and 7.4 when analysed by GraphPad Prism software version 4.0 San Diego, USA best fitted  the Makoid-2Banakar model (R  value greater than 0.98). The Korsmeyer-Peppas release exponent (n) ranged between 0.331 – 0.418, which confirmed diffusion as the principle mechanism of drug release. The release mechanism was further confirmed by calculating the ratio of exponents A/B ratio derived from the Kopcha model. KEYWORDS: Nanosponge, hydrogel, Makoid-Banakar, Kopcha model, Korsmeyer-Peppas model.Revised: 9/6/2010Submitted: 19/3/2010 Accepted: 14/7/2010Address for Correspondence:Kamla Pathak,  Rajiv Academy for Pharmacy, National Highway #2, P.O. Chhattikara, Mathura, Uttar Pradesh (INDIA) 281001E- mail:kamla_rap@yahoo.co.in; kamlapathak5@gmail.com25ABSTRACTInd J Pharm Edu Res, Jan-Mar, 2011/ Vol 45/ Issue 1Component N1 N2 N3 N4Drug : PVA : Ethyl cellulose (%w/w) 1 : 3 : 2 1 : 3 : 3 1 : 2 : 3 1 : 2 : 2 Dichloromethane (ml) 20 20 20 20 Distilled water (ml) 150 150 150 150 Z-average (nm) 230.1 470.0 420 342Polydispersity index 0.905 1.103 1.000 1.000Entrapment  efficiency (%) 90.43±0.09 94.45±0.08 81.8±0.16 91.55± 0.05Formulation codeTable 1: Formulation design and particle measurement data of econazole nitrate nanosponges prepared by emulsion solvent diffusion methodKamla et al.: Evaluation of the Kinetics and Mechanism of Drug Release from Econazole nitrate Nanosponge Loaded Carbapol Hydrogel26Ind J Pharm Edu Res, Jan-Mar, 2011/ Vol 45/ Issue 1(% w/w) F0 F1 F2 F3 F4 F5 F6 F7 Econazole nitrate nanosponges - 6.0 6.0 6.0 6.0 6.0 6.0 6.0 Econazole nitrate 1.0 -  -  - -  - - - Triethanolamine 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 Ethanol (95%v/v) 20 20 20 20 20 20 20 20 Propylene glycol - - 10  - 10 10 10 15 N-methyl-2- pyrrolidone - -  - 10 10 20 40 45 Carbapol 934 NF 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 Distilled water (q.s) 100 100 100 100 100 100 100 100Component Formulation CodeTable 2: Formulation design of econazole nitrate nanosponge loaded carbapol hydrogelsTable 3: Pharmacotechnical properties of EN nanosponge loaded carbapol hydrogelsHydrogel Viscosity  Drug content  pH code (cp) (%)F0 4720± 0.10 92.55± 0.80 6.54F1 7760± 0.56 82.34± 0.45 5.47F2 5680± 0.45 84.85± 0.95 6.44F3 6782± 0.67 86.21± 0.42 4.82F4 4440± 0.46 91.61± 0.80 5.51F5 5540± 0.28 89.43± 0.92 5.60F6 4580± 0.35 87.06± 0.47 6.25F7 4420± 0.12 92.57± 0.36 6.49Kamla et al.: Evaluation of the Kinetics and Mechanism of Drug Release from Econazole nitrate Nanosponge Loaded Carbapol Hydrogel27Ind J Pharm Edu Res, Jan-Mar, 2011/ Vol 45/ Issue 1Fig. 1. Scanning electron micrograph of (a) econazole nitrate nanosponges 1.00 KX and (b) surface view at 5.00KX(Fig 1a)(Fig 1b)Model Equation Zero order HiguchiKorsmeyer-PeppasKopchaMakoid-Banakar Q  = Q  + K tt 0 01/2Q  = Q  + K tt 0 HnQ  = K tt KP1/2Q  = At + Bttn (-ct)Q  =  K t et MBTable 4: Mathematical equations for the models used to describe release characteristics of econazole nitrate from carbapol hydrogels (a)(b)Kamla et al.: Evaluation of the Kinetics and Mechanism of Drug Release from Econazole nitrate Nanosponge Loaded Carbapol Hydrogel28Ind J Pharm Edu Res, Jan-Mar, 2011/ Vol 45/ Issue 1Fig. 2. In vitro release profiles of econazole nitrate loaded hydrogels in phosphate buffer pH 6.8Fig.  3. In vitro release profiles of econazole nitrate nanosponge loaded hydrogel in phosphate buffer pH 7.4Kamla et al.: Evaluation of the Kinetics and Mechanism of Drug Release from Econazole nitrate Nanosponge Loaded Carbapol Hydrogel29Ind J Pharm Edu Res, Jan-Mar, 2011/ Vol 45/ Issue 1F0 F1 F2 F3 F4 F5 F6 F72Zero order R  0.887 0.812 0.752 0.746 0.828 0.820 0.767 0.742 K  0.105  0.032 0.037  0.042 0.057  0.065 0.068 0.077 0SSR 1539 258.5 477.2 644.9 731.8 1013 1507 2213 2 Higuchi R 0.983 0.951 0.923 0.921 0.986 0.966 0.933 0.915 K  3.036  0.950 1.107 1.269 1.685 1.932 2.040 2.324 HSSR 236.1 68.17 148.0 200.9 136.2 192.9 437.1 731.3 2 Korsmeyer-Peppas R 0.989 0.958 0.959 0.988 0.968  0.987 0.968 0.947 K  5.716 1.669 3.556 4.148 4.176 5.063 6.679 7.141 KPN 0.408 0.418 0.334 0.331  0.370 0.362 0.331 0.340 SSR 147.3 58.35 79.74 106.7 59.58 75.78 207.9 452.9 2Kopcha R  0.912 0.968 0.966 0.933 0.904 0.966 0.933 0.904 A 3.036 0.950 1.107 1.389 1.685 1.932 2.040 2.564 B 0.0001  0.0001 00001 0.0001 00001 0.0001  00001 0.0001 SSR 236.1 68.17 148.0 222.9 136.2 192.9 437.2 824.2 2Makoid-Banakar R  0.990 0.992 0.978 0.980 0.992 0.994 0.980 0.975 K  6.943 0.431 2.035 2.265 2.812 3.241 4.238 3.250 MBN 0.362 0.734 0.478 0.487 0.465  0.470 0.447 0.537 C -0.0002 0.0012 0.0007 0.0007 0.0004 0.0006 0.0007 0.0007 SSR 131.6 11.76 43.02  50.03 34.90 33.45 129.0 211.6Kinetic model ParameterFormulation codeTable 5: Results of model fitting of drug release of nanosponge loaded hydrogel in phosphate buffer pH 6.8Kamla et al.: Evaluation of the Kinetics and Mechanism of Drug Release from Econazole nitrate Nanosponge Loaded Carbapol Hydrogel30Ind J Pharm Edu Res, Jan-Mar, 2011/ Vol 45/ Issue 1F0 F1 F2 F3 F4 F5 F6 F72Zero order R  0.864  0.846 0.783 0.762 0.838 0.826 0.785 0.763 K  0.093 0.028 0.036 0.039 0.057 0.064 0.066 0.069 0SSR 1479 160.6 380.3 513.6 680.2 927.4 1296 1592 2Higuchi R  0.980 0.959 0.943 0.930 0.970 0.969 0.947 0.935 K  2.712  0.829 1.068 1.175 1.676 1.888 1.981 2.079 HSSR 220.9 42.84 99.74 150.8 125.9 167.8 317.5 435.3 2Korsmeyer- Peppas R  0.990 0.961 0.963 0.957 0.979 0.984 0.975 0.973 K  5.738 1.162 2.639 3.277 3.197 4.392 5.778 6.931 KPN 0.3914 0.4507 0.3698 0.3532 0.4063 0.3782 0.3468 0.3285 SSR 1 05.7 40.47  64.58 92.76  89.12 83.95 148.1 184.4 2Kopcha R  0.979 0.959 0.942 0.921 0.970 0.969 0.947 0.935 A 2.803 0.829 1.096 1.288 1.676 1.888 1.981 2.079 B 0.0001 0.0001 00001 0.0001 00001 0.0001  00001 0.0001 SSR 234.5  42.84 101.1 171.5 125.9 167.8 317.5 435.3 2Makoid-Banakar R  0.9914 0.979 0.991 0.984 0.995  0.996  0.992 0.990 K  5.190 0.415 1.062 1.519 1.272 2.337 3.140 3.901 MBN  0.415 0.691 0.590 0.546  0.619  0.527 0.497 0.473 C 0.0010 0.0009 0.0009 0.0009 0.0008 0.0006 0.0007 0.0007 SSR 1 02.1 21.57 16.47 34.33 22.51 23.57 50.55 66.07Kinetic model ParameterFormulation codeTable 6: Results of model fitting of drug release of nanosponge loaded hydrogel in phosphate buffer pH 7.4REFERENCES1. 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A mathematical model to describe drug release from thin topical application. Int J Pharm. 1989; 56(3): 243-248.15. Khamanga SM, Parfitt N, Nyamuzhiwa HH, Walker RB. The evaluation of eudragit microcapsules manufactured by solvent evaporation using USP apparatus I. Dissol. Tech. 2009; 16(2):15-22.10. Osborne DW, Amann HA. Topical drug delivery formulation. New York: Marcel Dekker; 2000.Kamla et al.: Evaluation of the Kinetics and Mechanism of Drug Release from Econazole nitrate Nanosponge Loaded Carbapol Hydrogel31Ind J Pharm Edu Res, Jan-Mar, 2011/ Vol 45/ Issue 1

Evaluation of the kinetics and mechanism of drug release from Econazole nitrate nanosponge loaded Carbapol Hydrogel

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Evaluation of the kinetics and mechanism of drug release from Econazole nitrate nanosponge loaded Carbapol Hydrogel

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