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Cefaclor monohydrate loaded microemulsion formulation for topical application: Characterization with new developed UPLC method and stability study

Yıl 2019, Cilt: 23 Sayı: 3, 426 - 440, 27.06.2025

A. Alper Öztürk , Umay Merve Güven Bölgen

Öz

The purpose of this study was to formulate Cefaclor monohydrate (CEF) loaded microemulsion formulations with the help of pseudo-ternary phase diagrams for topical application. Additionally, in this study also a new ultra-performance liquid chromatography (UPLC) method was developed for the determination of CEF, which was not previously entered into the literature. The droplet size, polydispersity index, pH, rheology, drug content, FT IR, dissolution study and release kinetic study have been used in the characterization of microemulsion. The UPLC method developed was validated for linearity, specificity, precision, sensitivity, accuracy, range and robustness. Linearity was determined to be at a concentration range of 5-55 μg.mL-1. The method developed was decided to be precise due to RSD values of <2%. Recovery of the method was satisfactory owing to <2%RSD value. The drug content was found to be in the range of 99.54-100.01% in stability study, indicating the uniformity of the high drug content. The release of CEF from microemulsion showed conformity with the zero-order kinetics. The droplet size of the formulations were measured ranged in 170.6-174.4 nm. The droplet size distribution of the formulations were observed range in 0.154-0.150. The results showed that nano-sized and monodisperse formulations were prepared. The storage stability of CEF loaded optimum microemulsion was followed to ICH Q1(R2) at 251C/60%5% relative humidity up to six months. As a result of the stability study, microemulsion was found to be physically and chemically stable. According to the results, microemulsion formulation prepared have longer release times than the release of pure CEF.

Anahtar Kelimeler

Cefaclor monohydrate UPLC microemulsion stability study

Kaynakça

  • [1] Ribeiro AR, Sures B, Schmidt TC. Cephalosporin antibiotics in the aquatic environment: A critical review of occurrence, fate, ecotoxicity and removal technologies. Environ Pollut. 2018; 241: 1153-1166. [CrossRef]
  • [2] Lin CE, Chen HW, Lin EC, Lin KS, Huang HC. Optimization of separation and migration behavior of cephalosporins in capillary zone electrophoresis. J Chromatogr A. 2000; 879:197-210. [CrossRef]
  • [3] Ray P, Knowlton KF, Shang C, Xia K. Development and validation of a UPLC-MS/MS method to monitor cephapirin excretion in dairy cows following intramammary infusion. 2014; PLoS ONE 9(11): e112343. [CrossRef]
  • [4] Mohamed MA, Ali AH, Abdelfatah AM, Ahmed MO. Validation and comparative in-vitro dissolution studies of cefaclor in their powder for oral suspension dosage forms. Anal Chem Lett. 2018; 8(1): 88-103. [CrossRef]
  • [5] Zhao YY, Wu SP, Liu S, Zhang Y, Lin RC. Ultra-performance liquid chromatography–mass spectrometry as a sensitive and powerful technology in lipidomic applications. Chem Biol Interact. 2014; 220: 181-192. [CrossRef]
  • [6] Nordstrom A, O’Maille G, Qin C, Siuzdak G. Nonlinear data alignment for UPLC–MS and HPLC–MS based metabolomics: Quantitative analysis of endogenous and exogenous metabolites in human serum. Anal Chem. 2006; 78: 3289–3295. [CrossRef]
  • [7] Zhao YY, Lin RC. UPLC–MSE application in disease biomarker discovery: The discoveries in proteomics to metabolomics. Chem Biol Interact. 2014; 215: 7–16. [CrossRef]
  • [8] Joshi S. HPLC separation of antibiotics present in formulated and unformulated samples. J Pharm Biomed Anal. 2002; 28: 795-809. [CrossRef]
  • [9] El-Shaboury SR, Saleh GA, Mohamed FA, Rageh AH. Analysis of cephalosporin antibiotics. J Pharm Biomed Anal. 2007; 45(1):1-19. [CrossRef]
  • [10] Granados‐Soto V, Aguilar‐Cota ME, Reyes‐Garcia G, Medina‐Santillán R, Flores‐Murrieta FJ. Simple method for the determination of cefaclor in human plasma samples by HPLC. J Liq Chromatogr Relat Technol. 2003; 26(19): 3315-3323. [CrossRef]
  • [11] Lu Y, Wu K, Li L, He Y, Cui L, Liang N, Mu B. Characterization and evaluation of an oral microemulsion containing the antitumor diterpenoid compound ent-11alpha-hydroxy-15-oxo-kaur-16-en-19-oic-acid. Int J Nanomed. 2013; 8: 1879-1886. [CrossRef]
  • [12] Tang TT, Hu XB, Liao DH, Liu XY, Xiang DX. Mechanisms of microemulsion enhancing the oral bioavailability of puerarin: comparison between oil-in-water and water-in-oil microemulsions using the single-pass intestinal perfusion method and a chylomicron flow blocking approach. Int J Nanomed. 2013; 8: 4415-4426. [CrossRef]
  • [13] Roberts MS, Mohammed Y, Pastore MN, Namjoshi S, Yousef S, Alinaghi A, Haridass IN, Abd E, Leite-Silva VR, Benson HAE, Grice JE. Topical and cutaneous delivery using nanosystems. J Control Release. 2017; 247:86-105. [CrossRef]
  • [14] Öztürk AA, Yenilmez E, Yazan Y. Development and validation of high performance liquid chromatography (HPLC) modified method for dexketoprofen trometamol. Eur Int J Sci Tec. 2017;6(5):33-41.
  • [15] Öztürk AA, Güven UM, Yenilmez E. Flurbiprofen loaded gel based topical delivery system: Formulation and in vitro characterization with new developed UPLC method. Acta Pharm Sci. 2018;56(4):81-105. [CrossRef]
  • [16] Q2(R1) ICH Harmonised Tripartite Guideline (2014). Validation of Analytical Procedures: Text and Methodology.
  • [17] Uhrovcík J. Strategy for determination of LOD and LOQ values – Some basic aspects. Talanta. 2014;119:178-180. [CrossRef]
  • [18] Kogan A, Garti N. Microemulsions as transdermal drug delivery vehicles. Adv Col Int Sci. 2006;123:369-385. [CrossRef]
  • [19] Herman A, Herman AP. Essential oils and their constituents as skin penetration enhancer for transdermal drug delivery: A review. J Pharm Pharmacol. 2015;67(4): 473-485. [CrossRef]
  • [20] Huang YB, Lin YH, Lu TM, Wang RJ, Tsai YH, Wu PC. Transdermal delivery of capsaicin derivative-sodium nonivamide acetate using microemulsions as vehicles. Int J Pharm. 2008;349(1-2):206-211. [CrossRef]
  • [21] Goldberg-Cettina M, Liu P, Nightingale J, Kurihara-Bergstrom T. Enhanced transdermal delivery of estradiol in vitro using binary vehicles of isopropyl myristate and short-chain alkanols. Int J Pharm. 1995;114(2):237-245. [CrossRef]
  • [22] Liu CH, Chang FY, Hung DK. Terpene microemulsions for transdermal curcumin delivery: Effects of terpenes and cosurfactants. Col Surf B: Biointerfaces. 2011; 82(1):63-70. [CrossRef]
  • [23] Chen H, Chang X, Weng T, Zhao X, Gao Z, Yang Y, Yang X. A study of microemulsion systems for transdermal delivery of triptolide. J Control Release. 2004;98(3):427-436. [CrossRef]
  • [24] Okur NÜ, Yavaşoğlu A, Karasulu HY. Preparation and evaluation of microemulsion formulations of naproxen for dermal delivery. Chem Pharm Bull. 2014; 62(2): 135-143. [CrossRef]
  • [25] El Maghraby GM. Transdermal delivery of hydrocortisone from eucalyptus oil microemulsion: Effects of cosurfactants. Int J Pharm. 2008; 355(1-2):285-292. [CrossRef]
  • [26] Bharti SK, Kesavan K. Phase-transition W/O microemulsions for ocular delivery: Evaluation of antibacterial activity in the treatment of bacterial keratitis. Ocular Immuno Inflam. 2017; 25(4): 463-474. [CrossRef]
  • [27] Lawrence MJ, Rees GD. Microemulsion-based media as novel drug delivery systems. Adv Drug Del Rev. 2012; 64:175-193. [CrossRef]
  • [28] Schmalfuss U, Neubert R, Wohlrab W. Modification of drug penetration into human skin using microemulsions. J Control Release. 1997; 46(3): 279-285. [CrossRef]
  • [29] Öztürk AA, Martin Banderas L, Cayero Otero MD, Yenilmez E, Yazan Y. New Approach to hypertension treatment: Carvediol-loaded PLGA nanoparticles, preparation, in vitro characterization and gastrointestinal stability. Lat Am J Pharm. 2018; 37(9):1730-1741.
  • [30] Shah RR, Magdum CS, Patil SS, Naikwade NS. Preparation and evaluation of aceclofenac topical microemulsion. Iran J Pharm Res. 2010;9(1):5-11.
  • [31] Subramanian N, Ghosal SK, Acharya A, Moulik SP. Formulation and physicochemical characterization of microemulsion system using isopropyl myristate, medium-chain glyceride, polysorbate 80 and water. Chem Pharm Bull. 2005; 53(12):1530-1535. [CrossRef]
  • [32] Öztürk AA, Güven UM, Yenı̇lmez E, Senel B. Effects of different derivatives of Eudragit polymer on entrapment efficiency, in vitro dissolution, release kinetics and cell viability results on extended release flurbiprofen loaded nanomedicines. Lat Am J Pharm. 2018;37(10):1981-1992.
  • [33] Öztürk AA, Yenı̇lmez E, Senel B, Arslan R, Yazan Y. Dexketoprofen trometamol-loaded Kollidon® SR and Eudragit® RS 100 polymeric nanoparticles: Formulation and in vitro-in vivo evaluation. Lat Am J Pharm. 2017;36(11):2153-2165.
  • [34] Singh VK, Anis A, Al-Zahrani SM, Pal K. Microemulsions of sorbitans and its derivatives for iontophoretic drug delivery. Int J Electrochem Sci. 2015;10:2239-2252.

Yıl 2019, Cilt: 23 Sayı: 3, 426 - 440, 27.06.2025

A. Alper Öztürk , Umay Merve Güven Bölgen

Öz

Kaynakça

  • [1] Ribeiro AR, Sures B, Schmidt TC. Cephalosporin antibiotics in the aquatic environment: A critical review of occurrence, fate, ecotoxicity and removal technologies. Environ Pollut. 2018; 241: 1153-1166. [CrossRef]
  • [2] Lin CE, Chen HW, Lin EC, Lin KS, Huang HC. Optimization of separation and migration behavior of cephalosporins in capillary zone electrophoresis. J Chromatogr A. 2000; 879:197-210. [CrossRef]
  • [3] Ray P, Knowlton KF, Shang C, Xia K. Development and validation of a UPLC-MS/MS method to monitor cephapirin excretion in dairy cows following intramammary infusion. 2014; PLoS ONE 9(11): e112343. [CrossRef]
  • [4] Mohamed MA, Ali AH, Abdelfatah AM, Ahmed MO. Validation and comparative in-vitro dissolution studies of cefaclor in their powder for oral suspension dosage forms. Anal Chem Lett. 2018; 8(1): 88-103. [CrossRef]
  • [5] Zhao YY, Wu SP, Liu S, Zhang Y, Lin RC. Ultra-performance liquid chromatography–mass spectrometry as a sensitive and powerful technology in lipidomic applications. Chem Biol Interact. 2014; 220: 181-192. [CrossRef]
  • [6] Nordstrom A, O’Maille G, Qin C, Siuzdak G. Nonlinear data alignment for UPLC–MS and HPLC–MS based metabolomics: Quantitative analysis of endogenous and exogenous metabolites in human serum. Anal Chem. 2006; 78: 3289–3295. [CrossRef]
  • [7] Zhao YY, Lin RC. UPLC–MSE application in disease biomarker discovery: The discoveries in proteomics to metabolomics. Chem Biol Interact. 2014; 215: 7–16. [CrossRef]
  • [8] Joshi S. HPLC separation of antibiotics present in formulated and unformulated samples. J Pharm Biomed Anal. 2002; 28: 795-809. [CrossRef]
  • [9] El-Shaboury SR, Saleh GA, Mohamed FA, Rageh AH. Analysis of cephalosporin antibiotics. J Pharm Biomed Anal. 2007; 45(1):1-19. [CrossRef]
  • [10] Granados‐Soto V, Aguilar‐Cota ME, Reyes‐Garcia G, Medina‐Santillán R, Flores‐Murrieta FJ. Simple method for the determination of cefaclor in human plasma samples by HPLC. J Liq Chromatogr Relat Technol. 2003; 26(19): 3315-3323. [CrossRef]
  • [11] Lu Y, Wu K, Li L, He Y, Cui L, Liang N, Mu B. Characterization and evaluation of an oral microemulsion containing the antitumor diterpenoid compound ent-11alpha-hydroxy-15-oxo-kaur-16-en-19-oic-acid. Int J Nanomed. 2013; 8: 1879-1886. [CrossRef]
  • [12] Tang TT, Hu XB, Liao DH, Liu XY, Xiang DX. Mechanisms of microemulsion enhancing the oral bioavailability of puerarin: comparison between oil-in-water and water-in-oil microemulsions using the single-pass intestinal perfusion method and a chylomicron flow blocking approach. Int J Nanomed. 2013; 8: 4415-4426. [CrossRef]
  • [13] Roberts MS, Mohammed Y, Pastore MN, Namjoshi S, Yousef S, Alinaghi A, Haridass IN, Abd E, Leite-Silva VR, Benson HAE, Grice JE. Topical and cutaneous delivery using nanosystems. J Control Release. 2017; 247:86-105. [CrossRef]
  • [14] Öztürk AA, Yenilmez E, Yazan Y. Development and validation of high performance liquid chromatography (HPLC) modified method for dexketoprofen trometamol. Eur Int J Sci Tec. 2017;6(5):33-41.
  • [15] Öztürk AA, Güven UM, Yenilmez E. Flurbiprofen loaded gel based topical delivery system: Formulation and in vitro characterization with new developed UPLC method. Acta Pharm Sci. 2018;56(4):81-105. [CrossRef]
  • [16] Q2(R1) ICH Harmonised Tripartite Guideline (2014). Validation of Analytical Procedures: Text and Methodology.
  • [17] Uhrovcík J. Strategy for determination of LOD and LOQ values – Some basic aspects. Talanta. 2014;119:178-180. [CrossRef]
  • [18] Kogan A, Garti N. Microemulsions as transdermal drug delivery vehicles. Adv Col Int Sci. 2006;123:369-385. [CrossRef]
  • [19] Herman A, Herman AP. Essential oils and their constituents as skin penetration enhancer for transdermal drug delivery: A review. J Pharm Pharmacol. 2015;67(4): 473-485. [CrossRef]
  • [20] Huang YB, Lin YH, Lu TM, Wang RJ, Tsai YH, Wu PC. Transdermal delivery of capsaicin derivative-sodium nonivamide acetate using microemulsions as vehicles. Int J Pharm. 2008;349(1-2):206-211. [CrossRef]
  • [21] Goldberg-Cettina M, Liu P, Nightingale J, Kurihara-Bergstrom T. Enhanced transdermal delivery of estradiol in vitro using binary vehicles of isopropyl myristate and short-chain alkanols. Int J Pharm. 1995;114(2):237-245. [CrossRef]
  • [22] Liu CH, Chang FY, Hung DK. Terpene microemulsions for transdermal curcumin delivery: Effects of terpenes and cosurfactants. Col Surf B: Biointerfaces. 2011; 82(1):63-70. [CrossRef]
  • [23] Chen H, Chang X, Weng T, Zhao X, Gao Z, Yang Y, Yang X. A study of microemulsion systems for transdermal delivery of triptolide. J Control Release. 2004;98(3):427-436. [CrossRef]
  • [24] Okur NÜ, Yavaşoğlu A, Karasulu HY. Preparation and evaluation of microemulsion formulations of naproxen for dermal delivery. Chem Pharm Bull. 2014; 62(2): 135-143. [CrossRef]
  • [25] El Maghraby GM. Transdermal delivery of hydrocortisone from eucalyptus oil microemulsion: Effects of cosurfactants. Int J Pharm. 2008; 355(1-2):285-292. [CrossRef]
  • [26] Bharti SK, Kesavan K. Phase-transition W/O microemulsions for ocular delivery: Evaluation of antibacterial activity in the treatment of bacterial keratitis. Ocular Immuno Inflam. 2017; 25(4): 463-474. [CrossRef]
  • [27] Lawrence MJ, Rees GD. Microemulsion-based media as novel drug delivery systems. Adv Drug Del Rev. 2012; 64:175-193. [CrossRef]
  • [28] Schmalfuss U, Neubert R, Wohlrab W. Modification of drug penetration into human skin using microemulsions. J Control Release. 1997; 46(3): 279-285. [CrossRef]
  • [29] Öztürk AA, Martin Banderas L, Cayero Otero MD, Yenilmez E, Yazan Y. New Approach to hypertension treatment: Carvediol-loaded PLGA nanoparticles, preparation, in vitro characterization and gastrointestinal stability. Lat Am J Pharm. 2018; 37(9):1730-1741.
  • [30] Shah RR, Magdum CS, Patil SS, Naikwade NS. Preparation and evaluation of aceclofenac topical microemulsion. Iran J Pharm Res. 2010;9(1):5-11.
  • [31] Subramanian N, Ghosal SK, Acharya A, Moulik SP. Formulation and physicochemical characterization of microemulsion system using isopropyl myristate, medium-chain glyceride, polysorbate 80 and water. Chem Pharm Bull. 2005; 53(12):1530-1535. [CrossRef]
  • [32] Öztürk AA, Güven UM, Yenı̇lmez E, Senel B. Effects of different derivatives of Eudragit polymer on entrapment efficiency, in vitro dissolution, release kinetics and cell viability results on extended release flurbiprofen loaded nanomedicines. Lat Am J Pharm. 2018;37(10):1981-1992.
  • [33] Öztürk AA, Yenı̇lmez E, Senel B, Arslan R, Yazan Y. Dexketoprofen trometamol-loaded Kollidon® SR and Eudragit® RS 100 polymeric nanoparticles: Formulation and in vitro-in vivo evaluation. Lat Am J Pharm. 2017;36(11):2153-2165.
  • [34] Singh VK, Anis A, Al-Zahrani SM, Pal K. Microemulsions of sorbitans and its derivatives for iontophoretic drug delivery. Int J Electrochem Sci. 2015;10:2239-2252.
Toplam 34 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Farmasotik Biyoteknoloji
Bölüm Articles
Yazarlar

A. Alper Öztürk

Umay Merve Güven Bölgen

Yayımlanma Tarihi 27 Haziran 2025
Yayımlandığı Sayı Yıl 2019 Cilt: 23 Sayı: 3

Kaynak Göster

APA Öztürk, A. A., & Güven Bölgen, U. M. (2025). Cefaclor monohydrate loaded microemulsion formulation for topical application: Characterization with new developed UPLC method and stability study. Journal of Research in Pharmacy, 23(3), 426-440.
AMA Öztürk AA, Güven Bölgen UM. Cefaclor monohydrate loaded microemulsion formulation for topical application: Characterization with new developed UPLC method and stability study. J. Res. Pharm. Haziran 2025;23(3):426-440.
Chicago Öztürk, A. Alper, ve Umay Merve Güven Bölgen. “Cefaclor Monohydrate Loaded Microemulsion Formulation for Topical Application: Characterization With New Developed UPLC Method and Stability Study”. Journal of Research in Pharmacy 23, sy. 3 (Haziran 2025): 426-40.
EndNote Öztürk AA, Güven Bölgen UM (01 Haziran 2025) Cefaclor monohydrate loaded microemulsion formulation for topical application: Characterization with new developed UPLC method and stability study. Journal of Research in Pharmacy 23 3 426–440.
IEEE A. A. Öztürk ve U. M. Güven Bölgen, “Cefaclor monohydrate loaded microemulsion formulation for topical application: Characterization with new developed UPLC method and stability study”, J. Res. Pharm., c. 23, sy. 3, ss. 426–440, 2025.
ISNAD Öztürk, A. Alper - Güven Bölgen, Umay Merve. “Cefaclor Monohydrate Loaded Microemulsion Formulation for Topical Application: Characterization With New Developed UPLC Method and Stability Study”. Journal of Research in Pharmacy 23/3 (Haziran 2025), 426-440.
JAMA Öztürk AA, Güven Bölgen UM. Cefaclor monohydrate loaded microemulsion formulation for topical application: Characterization with new developed UPLC method and stability study. J. Res. Pharm. 2025;23:426–440.
MLA Öztürk, A. Alper ve Umay Merve Güven Bölgen. “Cefaclor Monohydrate Loaded Microemulsion Formulation for Topical Application: Characterization With New Developed UPLC Method and Stability Study”. Journal of Research in Pharmacy, c. 23, sy. 3, 2025, ss. 426-40.
Vancouver Öztürk AA, Güven Bölgen UM. Cefaclor monohydrate loaded microemulsion formulation for topical application: Characterization with new developed UPLC method and stability study. J. Res. Pharm. 2025;23(3):426-40.