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QbD-steered fabrication of lisinopril ion-pair gel for improved skin permeability and bioavailability in rabbits

Yıl 2023, Cilt: 27 Sayı: 6, 2425 - 2442, 28.06.2025

Vijaykumar Pawar Harinath More Manish Bhatia

Öz

Lisinopril belongs to BCS class III having high solubility and low permeability. Reportedly, the oral bioavailability of lisinopril is 25 to 30% and its effectiveness is limited due to poor permeability. Hence, the current investigation is aimed to formulate transdermal ion-pair gel using a permeation enhancer for enhanced delivery of lisinopril across the stratum corneum and evaluate pharmacokinetics of lisinopril in rabbits. The formation of ion-pair is corroborated using Fourier Transform Infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), X-ray Diffraction (XRD), zeta potential, particle size analysis, oil/water partition coefficient study, etc. Optimization of the formulation was done using 32 factorial designs. Total nine batches (F1-F9) were prepared and the effect of propylene glycol (mL; X1) and carbopol 934 (%; X2) was investigated on gel viscosity (Y1) and permeability through rabbit’s skin at 8h (Y2). Propylene glycol exhibited a non-significant (p>0.05) effect on both gel viscosity and skin permeability whereas carbopol 934 demonstrated significant (p<0.05) positive and negative effects on both, respectively. The viscosity of all the lisinopril ion-pair gel (F1-F9) was ranging between 17.24 ± 2.16 Pa.s (Batch F9) to 7.54 ± 1.34 Pa.s (Batch F4). Ex-vivo permeability of all the prepared batches (F1-F9) across excised rabbit’s skin was ranging between 85.93 ± 1.26% (Batch F4) to 62.17 ± 1.57% (Batch F9). Remarkably, optimized formulation (F4) exhibited 1.7 folds improvement in skin permeability and 2.4 folds improvement in bioavailability than plain lisinopril gel. These findings demonstrate that ion pair formation is a promising strategy for significantly improving the skin permeability of lisinopril.

Anahtar Kelimeler

Ion-pair formation permeation enhancer topical drug delivery Carbopol 934 Angiotensin Converting Enzyme

Kaynakça

  • [1] Helal F, Lane ME. Transdermal delivery of angiotensin converting enzyme inhibitors. Eur J Pharm Biopharm. 2014; 88(1): 1–7. https://doi.org/10.1016/j.ejpb.2014.03.007
  • [2] Armayor G, Lopez M. Lisinopril: a new angiotensin converting enzyme inhibitor. Drug Intell Clin Pharm. 1988; 22(5): 365–372. https://doi.org/10.1177/106002808802200501
  • [3] Dilsizian V, Eckelman WC, Loredo ML, Jagoda EM, Shirani J. Evidence for tissue angiotensin-converting enzyme in explanted hearts of ischemic cardiomyopathy using targeted radiotracer technique. J Nucl Med. 2007; 48(2): 182–187.
  • [4] Chandrashekhar Y, Narula J. Exposing ACE up the sleeve. J Nucl Med. 2007; 48(2): 173–174.
  • [5] Femia FJ, Maresca KP, Hillier SM, Zimmerman CN, Joyal JL, Barrett JA, Aras O, Dilsizian V, Eckelman WC, Babich JW. Synthesis and evaluation of a series of 99m Tc (CO)3+ lisinopril complexes for in vivo imaging of angiotensin converting enzyme expression. J Nucl Med. 2008; 49(6): 970–977. https://doi.org/10.2967/jnumed.107.049064
  • [6] Jeong WY, Kwon M, Choi HE, Kim KS. Recent advances in transdermal drug delivery systems: A review. Biomater Res. 2021; 25: 24. https://doi.org/10.1186/s40824-021-00226-6
  • [7] Gisby J, Bryant J. Efficacy of a new cream formulation of mupirocin: comparison with oral and topical agents in experimental skin infections. Antimicrob Agents Chemother. 2000; 44(2): 255–260. https://doi.org/10.1128/AAC.44.2.255-260.2000
  • [8] Verma A, Singh S, Kaur R, Kumar A, Jain UK. Formulation, optimization and evaluation of clobetasol propionate gel. Int J Pharm Pharm Sci. 2013; 5(4): 666–674.
  • [9] Dantas MG, Reis SA, Damasceno CM, Rolim LA, Rolim-Neto PJ, Carvalho FO, Quintans-Junior LJ, Almeida JR. Development and evaluation of stability of a gel formulation containing the monoterpene borneol. The Sci World J. 2016; 2016: 7394685. https://doi.org/10.1155/2016/7394685
  • [10] Karadzovska D, Brooks JD, Monteiro-Riviere NA, Riviere JE. Predicting skin permeability from complex vehicles. Adv Drug Deliv Rev. 2013; 65(2): 265–277. https://doi.org/10.1016/j.addr.2012.01.019
  • [11] Shah VP, Behl CR, Flynn GL, Higuchi WI, Schaefer H. Principles and criteria in the development and optimization of topical therapeutic products. Skin Pharmacol. 1993; 6(1): 72–80. https://doi.org/10.1159/000211090
  • [12] Patel NA, Patel NJ, Patel RP. Formulation and evaluation of curcumin gel for topical application. Pharm Dev Technol. 2009; 14(1): 80–89. https://doi.org/10.1080/10837450802409438
  • [13] Fox LT, Gerber M, Plessis JD, Hamman JH. Transdermal drug delivery enhancement by compounds of natural origin. Molecules. 2011; 16(12): 10507–10540. https://doi.org/10.3390/molecules161210507
  • [14] Vijaya C, Bingi M, Vigneshwaran LV. Transdermal delivery of venlafaxine hydrochloride: The effects of enhancers on permeation across pig ear skin. Indian J Pharm Sci. 2011; 73(4): 456–459. https://doi.org/10.4103/0250-474X.95650
  • [15] Shah SNH, Tahir MA, Safdar A, Riyaz A, Shahzad Y, Rabbani M, Karim S, Murtaza G. Effect of permeation enhancers on the release behavior and permeation kinetics of novel tramadol lotions. Trop J Pharm Res. 2013; 12(1): 27–32. https://doi.org/10.4314/tjpr.v12i1.5
  • [16] Cristofoli M, Kung CP, Hadgraft J, Lane ME, Sil BC. Ion pairs for transdermal and dermal drug delivery: A review. Pharmaceutics. 2021; 13(6): 909. https://doi.org/10.3390/pharmaceutics13060909
  • [17] Adjei A, Rao S, Garren J, Menon G, Vadnere M. Effect of ion pairing on 1-octanol-water partitioning of peptide drugs. I: The nanopeptide leuprolide acetate. Int J Pharm. 1993; 90: 141–149. https://doi.org/10.1016/0378-5173(93)90150-E
  • [18] Brady J, Durig T, Lee PI, Li J.-X. Polymer properties and characterization. In: Qiu Y, Zhang GGZ, Mantri RV, Chen Y, Yu L. (Eds). Developing Solid Oral Dosage Forms, Pharmaceutical Theory and Practice. Elsevier, 2nd ed.: Academic Press, 2017, pp.181–223. https://doi.org/10.1016/B978-0-12-802447-8.00007-8
  • [19] Nadaf SJ, Killedar SG. Curcumin nanocochleates: Use of design of experiments, solid state characterization, in vitro apoptosis and cytotoxicity against breast cancer MCF-7 cells. J Drug Deliv Sci Technol. 2018; 47: 337–350. https://doi.org/10.1016/j.jddst.2018.06.026
  • [20] Shamsheer AS, Sabareesh M, Khan PR, Sai Krishna P, Sudheer B. Formulation and evaluation of lisinopril dihydrate transdermal proniosomal gels. J Appl Pharm Sci. 2011; 1(8): 181–185.
  • [21] Lozoya-Agullo I, González-Álvarez I, González-Álvarez M, Merino-Sanjuán M, Bermejo M. Development of an ion-pair to improve the colon permeability of a low permeability drug: Atenolol. Eur J Pharm Sci. 2016; 10(93): 334–340. https://doi.org/10.1016/j.ejps.2016.08.035
  • [22] Engelhardt G. Pharmacology of meloxicam, a new non-steroidal anti-inflammatory drug with an improved safety profile through preferential inhibition of COX-2. Br J Rheumatol. 1996; 35(Suppl 1): 4–12. https://doi.org/10.1093/rheumatology/35.suppl_1.4
  • [23] Jiang Q, Wang J, Ma P, Liu C, Sun M, Sun Y, He Z. Ion-pair formation combined with a penetration enhancer as a dual strategy to improve the transdermal delivery of meloxicam. Drug Deliv Transl Res. 2018; 8(1): 64–72. https://doi.org/10.1007/s13346-017-0434-z
  • [24] Nadaf SJ, Jadhav A, Killedar SG. Mung bean (Vigna radiata) porous starch for solubility and dissolution enhancement of poorly soluble drug by solid dispersion. Int J Biol Macromol. 2021; 167: 345–357. https://doi.org/10.1016/j.ijbiomac.2020.11.172
  • [25] Ma H, Guo D, Fan Y, Wang J, Cheng J, Zhang X. Paeonol-loaded ethosomes as topical delivery carriers: Design, preparation and evaluation. Molecules. 2018; 23: 1756. https://doi.org/10.3390/molecules23071756
  • [26] Bhagwat DA, Swami PA, Nadaf SJ, Choudhari PB, Kumbar VM, More HN, Killedar SG, Kawtikwar PS. Capsaicin loaded solid SNEDDS for enhanced bioavailability and anticancer activity: In-vitro, in-silico, and in-vivo characterization. J Pharm Sci. 2021; 110: 280–291. https://doi.org/10.1016/j.xphs.2020.10.020
  • [27] Barkin L. Topical nonsteroidal anti-inflammatory drugs: The importance of drug, delivery, and therapeutic outcomes. Am J Ther. 2015; 22: 388–407. https://doi.org/1097/MJT.0b013e3182459abd
  • [28] Rajan R, Vasudevan D. Effect of permeation enhancers on the penetration mechanism of transfersomal gel of ketoconazole. J Adv Pharm Technol Res. 2012; 3(7): 112–116. https://doi.org/10.4103/2231-4040.97286
  • [29] Qushawy M, Nasr A, Abd-Alhaseeb M, Swidan S. Design, optimization and characterization of a transfersomal gel using miconazole nitrate for the treatment of candida skin infection. Pharmaceutics. 2018; 10: 26–30. https://doi.org/10.3390/pharmaceutics10010026
  • [30] Mulani H, Bhise K. QbD Approach in the formulation and evaluation of miconazole nitrate loaded ethosomal cream-o-gel. Int Res J Pharm Sci. 2017; 8: 1–37.
  • [31] Wadher K, Dabre S, Gaidhane A, Trivedi S, Umekar M. Evaluation of antipsoriatic activity of gel containing Pongamia pinnata extract on imiquimod-induced psoriasis. Clin Phytosci. 2021; 7: 20. https://doi.org/10.1186/s40816-021-00256-6
  • [32] Cui H, Quan P, Zhao H, Wen X, Song W, Xiao Y, Zhao Y, Fang L. Mechanism of ion-pair strategy in modulating skin permeability of zaltoprofen: insight from molecular level resolution based on molecular modeling and confocal laser scanning microscopy. J Pharm Sci. 2015; 104: 3395–3403. https://doi.org/10.1002/jps.24543
  • [33] Pradad GR, Srinivas BP, Ramana MV. Validated RP-HPLC method for the estimation of drospirenone in formulation. Int J Res Pharm Biomed Sci. 2011; 2: 1341–1345.
  • [34] Singh S, Parhi R, Garg A. Formulation of topical bioadhesive gel of aceclofenac using 3-level factorial design. Iran J Pharm Res. 2011; 10(3): 435–445.
  • [35] Jantharaprapap R, Stagni G. Effects of penetration enhancers on in vitro permeability of meloxicam gels. Int J Pharm. 2007; 343(1–2): 26–33. https://doi.org/10.1016/j.ijpharm.2007.04.011
  • [36] Sing P, Roberts MS. Skin permeability and local tissue concentrations of nonsteroidal anti-inflammatory drugs after topical application. J Pharmacol Exp Ther. 1993; 268(1): 144–151.
  • [37] Lulekal E, Tesfaye S, Gebrechristos S, Dires K, Zenebe T, Zegeye N, Feleke G, Kassahun A, Shiferaw Y, Mekonnen A. Phytochemical analysis and evaluation of skin irritation, acute and sub-acute toxicity of Cymbopogon citratus essential oil in mice and rabbits. Toxicol Rep. 2019; 6: 1289–1294. https://doi.org/10.1016/j.toxrep.2019.11.002
  • [38] Vats R, Murthy AN, Ravi PR. Simple, rapid and validated LC determination of lopinavir in rat plasma and its application in pharmacokinetic studies. Sci Pharm. 2011; 79: 849–863. https://doi.org/10.3797/scipharm.1107-24
  • [39] Ansari H, Singh P. Formulation and in-vivo evaluation of novel topical gel of lopinavir for targeting HIV. Curr HIV Res. 2018; 16(4): 270–279. https://doi.org/10.2174/1570162X16666180924101650

Yıl 2023, Cilt: 27 Sayı: 6, 2425 - 2442, 28.06.2025

Vijaykumar Pawar Harinath More Manish Bhatia

Öz

Kaynakça

  • [1] Helal F, Lane ME. Transdermal delivery of angiotensin converting enzyme inhibitors. Eur J Pharm Biopharm. 2014; 88(1): 1–7. https://doi.org/10.1016/j.ejpb.2014.03.007
  • [2] Armayor G, Lopez M. Lisinopril: a new angiotensin converting enzyme inhibitor. Drug Intell Clin Pharm. 1988; 22(5): 365–372. https://doi.org/10.1177/106002808802200501
  • [3] Dilsizian V, Eckelman WC, Loredo ML, Jagoda EM, Shirani J. Evidence for tissue angiotensin-converting enzyme in explanted hearts of ischemic cardiomyopathy using targeted radiotracer technique. J Nucl Med. 2007; 48(2): 182–187.
  • [4] Chandrashekhar Y, Narula J. Exposing ACE up the sleeve. J Nucl Med. 2007; 48(2): 173–174.
  • [5] Femia FJ, Maresca KP, Hillier SM, Zimmerman CN, Joyal JL, Barrett JA, Aras O, Dilsizian V, Eckelman WC, Babich JW. Synthesis and evaluation of a series of 99m Tc (CO)3+ lisinopril complexes for in vivo imaging of angiotensin converting enzyme expression. J Nucl Med. 2008; 49(6): 970–977. https://doi.org/10.2967/jnumed.107.049064
  • [6] Jeong WY, Kwon M, Choi HE, Kim KS. Recent advances in transdermal drug delivery systems: A review. Biomater Res. 2021; 25: 24. https://doi.org/10.1186/s40824-021-00226-6
  • [7] Gisby J, Bryant J. Efficacy of a new cream formulation of mupirocin: comparison with oral and topical agents in experimental skin infections. Antimicrob Agents Chemother. 2000; 44(2): 255–260. https://doi.org/10.1128/AAC.44.2.255-260.2000
  • [8] Verma A, Singh S, Kaur R, Kumar A, Jain UK. Formulation, optimization and evaluation of clobetasol propionate gel. Int J Pharm Pharm Sci. 2013; 5(4): 666–674.
  • [9] Dantas MG, Reis SA, Damasceno CM, Rolim LA, Rolim-Neto PJ, Carvalho FO, Quintans-Junior LJ, Almeida JR. Development and evaluation of stability of a gel formulation containing the monoterpene borneol. The Sci World J. 2016; 2016: 7394685. https://doi.org/10.1155/2016/7394685
  • [10] Karadzovska D, Brooks JD, Monteiro-Riviere NA, Riviere JE. Predicting skin permeability from complex vehicles. Adv Drug Deliv Rev. 2013; 65(2): 265–277. https://doi.org/10.1016/j.addr.2012.01.019
  • [11] Shah VP, Behl CR, Flynn GL, Higuchi WI, Schaefer H. Principles and criteria in the development and optimization of topical therapeutic products. Skin Pharmacol. 1993; 6(1): 72–80. https://doi.org/10.1159/000211090
  • [12] Patel NA, Patel NJ, Patel RP. Formulation and evaluation of curcumin gel for topical application. Pharm Dev Technol. 2009; 14(1): 80–89. https://doi.org/10.1080/10837450802409438
  • [13] Fox LT, Gerber M, Plessis JD, Hamman JH. Transdermal drug delivery enhancement by compounds of natural origin. Molecules. 2011; 16(12): 10507–10540. https://doi.org/10.3390/molecules161210507
  • [14] Vijaya C, Bingi M, Vigneshwaran LV. Transdermal delivery of venlafaxine hydrochloride: The effects of enhancers on permeation across pig ear skin. Indian J Pharm Sci. 2011; 73(4): 456–459. https://doi.org/10.4103/0250-474X.95650
  • [15] Shah SNH, Tahir MA, Safdar A, Riyaz A, Shahzad Y, Rabbani M, Karim S, Murtaza G. Effect of permeation enhancers on the release behavior and permeation kinetics of novel tramadol lotions. Trop J Pharm Res. 2013; 12(1): 27–32. https://doi.org/10.4314/tjpr.v12i1.5
  • [16] Cristofoli M, Kung CP, Hadgraft J, Lane ME, Sil BC. Ion pairs for transdermal and dermal drug delivery: A review. Pharmaceutics. 2021; 13(6): 909. https://doi.org/10.3390/pharmaceutics13060909
  • [17] Adjei A, Rao S, Garren J, Menon G, Vadnere M. Effect of ion pairing on 1-octanol-water partitioning of peptide drugs. I: The nanopeptide leuprolide acetate. Int J Pharm. 1993; 90: 141–149. https://doi.org/10.1016/0378-5173(93)90150-E
  • [18] Brady J, Durig T, Lee PI, Li J.-X. Polymer properties and characterization. In: Qiu Y, Zhang GGZ, Mantri RV, Chen Y, Yu L. (Eds). Developing Solid Oral Dosage Forms, Pharmaceutical Theory and Practice. Elsevier, 2nd ed.: Academic Press, 2017, pp.181–223. https://doi.org/10.1016/B978-0-12-802447-8.00007-8
  • [19] Nadaf SJ, Killedar SG. Curcumin nanocochleates: Use of design of experiments, solid state characterization, in vitro apoptosis and cytotoxicity against breast cancer MCF-7 cells. J Drug Deliv Sci Technol. 2018; 47: 337–350. https://doi.org/10.1016/j.jddst.2018.06.026
  • [20] Shamsheer AS, Sabareesh M, Khan PR, Sai Krishna P, Sudheer B. Formulation and evaluation of lisinopril dihydrate transdermal proniosomal gels. J Appl Pharm Sci. 2011; 1(8): 181–185.
  • [21] Lozoya-Agullo I, González-Álvarez I, González-Álvarez M, Merino-Sanjuán M, Bermejo M. Development of an ion-pair to improve the colon permeability of a low permeability drug: Atenolol. Eur J Pharm Sci. 2016; 10(93): 334–340. https://doi.org/10.1016/j.ejps.2016.08.035
  • [22] Engelhardt G. Pharmacology of meloxicam, a new non-steroidal anti-inflammatory drug with an improved safety profile through preferential inhibition of COX-2. Br J Rheumatol. 1996; 35(Suppl 1): 4–12. https://doi.org/10.1093/rheumatology/35.suppl_1.4
  • [23] Jiang Q, Wang J, Ma P, Liu C, Sun M, Sun Y, He Z. Ion-pair formation combined with a penetration enhancer as a dual strategy to improve the transdermal delivery of meloxicam. Drug Deliv Transl Res. 2018; 8(1): 64–72. https://doi.org/10.1007/s13346-017-0434-z
  • [24] Nadaf SJ, Jadhav A, Killedar SG. Mung bean (Vigna radiata) porous starch for solubility and dissolution enhancement of poorly soluble drug by solid dispersion. Int J Biol Macromol. 2021; 167: 345–357. https://doi.org/10.1016/j.ijbiomac.2020.11.172
  • [25] Ma H, Guo D, Fan Y, Wang J, Cheng J, Zhang X. Paeonol-loaded ethosomes as topical delivery carriers: Design, preparation and evaluation. Molecules. 2018; 23: 1756. https://doi.org/10.3390/molecules23071756
  • [26] Bhagwat DA, Swami PA, Nadaf SJ, Choudhari PB, Kumbar VM, More HN, Killedar SG, Kawtikwar PS. Capsaicin loaded solid SNEDDS for enhanced bioavailability and anticancer activity: In-vitro, in-silico, and in-vivo characterization. J Pharm Sci. 2021; 110: 280–291. https://doi.org/10.1016/j.xphs.2020.10.020
  • [27] Barkin L. Topical nonsteroidal anti-inflammatory drugs: The importance of drug, delivery, and therapeutic outcomes. Am J Ther. 2015; 22: 388–407. https://doi.org/1097/MJT.0b013e3182459abd
  • [28] Rajan R, Vasudevan D. Effect of permeation enhancers on the penetration mechanism of transfersomal gel of ketoconazole. J Adv Pharm Technol Res. 2012; 3(7): 112–116. https://doi.org/10.4103/2231-4040.97286
  • [29] Qushawy M, Nasr A, Abd-Alhaseeb M, Swidan S. Design, optimization and characterization of a transfersomal gel using miconazole nitrate for the treatment of candida skin infection. Pharmaceutics. 2018; 10: 26–30. https://doi.org/10.3390/pharmaceutics10010026
  • [30] Mulani H, Bhise K. QbD Approach in the formulation and evaluation of miconazole nitrate loaded ethosomal cream-o-gel. Int Res J Pharm Sci. 2017; 8: 1–37.
  • [31] Wadher K, Dabre S, Gaidhane A, Trivedi S, Umekar M. Evaluation of antipsoriatic activity of gel containing Pongamia pinnata extract on imiquimod-induced psoriasis. Clin Phytosci. 2021; 7: 20. https://doi.org/10.1186/s40816-021-00256-6
  • [32] Cui H, Quan P, Zhao H, Wen X, Song W, Xiao Y, Zhao Y, Fang L. Mechanism of ion-pair strategy in modulating skin permeability of zaltoprofen: insight from molecular level resolution based on molecular modeling and confocal laser scanning microscopy. J Pharm Sci. 2015; 104: 3395–3403. https://doi.org/10.1002/jps.24543
  • [33] Pradad GR, Srinivas BP, Ramana MV. Validated RP-HPLC method for the estimation of drospirenone in formulation. Int J Res Pharm Biomed Sci. 2011; 2: 1341–1345.
  • [34] Singh S, Parhi R, Garg A. Formulation of topical bioadhesive gel of aceclofenac using 3-level factorial design. Iran J Pharm Res. 2011; 10(3): 435–445.
  • [35] Jantharaprapap R, Stagni G. Effects of penetration enhancers on in vitro permeability of meloxicam gels. Int J Pharm. 2007; 343(1–2): 26–33. https://doi.org/10.1016/j.ijpharm.2007.04.011
  • [36] Sing P, Roberts MS. Skin permeability and local tissue concentrations of nonsteroidal anti-inflammatory drugs after topical application. J Pharmacol Exp Ther. 1993; 268(1): 144–151.
  • [37] Lulekal E, Tesfaye S, Gebrechristos S, Dires K, Zenebe T, Zegeye N, Feleke G, Kassahun A, Shiferaw Y, Mekonnen A. Phytochemical analysis and evaluation of skin irritation, acute and sub-acute toxicity of Cymbopogon citratus essential oil in mice and rabbits. Toxicol Rep. 2019; 6: 1289–1294. https://doi.org/10.1016/j.toxrep.2019.11.002
  • [38] Vats R, Murthy AN, Ravi PR. Simple, rapid and validated LC determination of lopinavir in rat plasma and its application in pharmacokinetic studies. Sci Pharm. 2011; 79: 849–863. https://doi.org/10.3797/scipharm.1107-24
  • [39] Ansari H, Singh P. Formulation and in-vivo evaluation of novel topical gel of lopinavir for targeting HIV. Curr HIV Res. 2018; 16(4): 270–279. https://doi.org/10.2174/1570162X16666180924101650
Toplam 39 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Eczacılık ve İlaç Bilimleri (Diğer)
Bölüm Articles
Yazarlar

Vijaykumar Pawar 0000-0002-7369-5355

Harinath More 0000-0001-6721-727X

Manish Bhatia 0000-0003-4045-5280

Yayımlanma Tarihi 28 Haziran 2025
Yayımlandığı Sayı Yıl 2023 Cilt: 27 Sayı: 6

Kaynak Göster

APA Pawar, V., More, H., & Bhatia, M. (2025). QbD-steered fabrication of lisinopril ion-pair gel for improved skin permeability and bioavailability in rabbits. Journal of Research in Pharmacy, 27(6), 2425-2442.
AMA Pawar V, More H, Bhatia M. QbD-steered fabrication of lisinopril ion-pair gel for improved skin permeability and bioavailability in rabbits. J. Res. Pharm. Temmuz 2025;27(6):2425-2442.
Chicago Pawar, Vijaykumar, Harinath More, ve Manish Bhatia. “QbD-Steered Fabrication of Lisinopril Ion-Pair Gel for Improved Skin Permeability and Bioavailability in Rabbits”. Journal of Research in Pharmacy 27, sy. 6 (Temmuz 2025): 2425-42.
EndNote Pawar V, More H, Bhatia M (01 Temmuz 2025) QbD-steered fabrication of lisinopril ion-pair gel for improved skin permeability and bioavailability in rabbits. Journal of Research in Pharmacy 27 6 2425–2442.
IEEE V. Pawar, H. More, ve M. Bhatia, “QbD-steered fabrication of lisinopril ion-pair gel for improved skin permeability and bioavailability in rabbits”, J. Res. Pharm., c. 27, sy. 6, ss. 2425–2442, 2025.
ISNAD Pawar, Vijaykumar vd. “QbD-Steered Fabrication of Lisinopril Ion-Pair Gel for Improved Skin Permeability and Bioavailability in Rabbits”. Journal of Research in Pharmacy 27/6 (Temmuz 2025), 2425-2442.
JAMA Pawar V, More H, Bhatia M. QbD-steered fabrication of lisinopril ion-pair gel for improved skin permeability and bioavailability in rabbits. J. Res. Pharm. 2025;27:2425–2442.
MLA Pawar, Vijaykumar vd. “QbD-Steered Fabrication of Lisinopril Ion-Pair Gel for Improved Skin Permeability and Bioavailability in Rabbits”. Journal of Research in Pharmacy, c. 27, sy. 6, 2025, ss. 2425-42.
Vancouver Pawar V, More H, Bhatia M. QbD-steered fabrication of lisinopril ion-pair gel for improved skin permeability and bioavailability in rabbits. J. Res. Pharm. 2025;27(6):2425-42.