Gel Formulation and an In-vitro Kinetic Permeation Release Study of Cefixime Trihydrate and Chlorpheniramine Maleate (CCM): Cefixime Trihydrate and Chlorpheniramine Maleate (CCM)

Sadia Rafique; Farah Sattar; Amina` Habib; Saif`` Babar; Abdul Qader; Mariam Davis; Sana`` Javed`; Muhammad Usama Ibrahim Khan; Muhammad Haris; Hamza Tariq; . Afnan

doi:10.54393/pjhs.v4i11.825

Authors

Sadia Rafique College of Pharmacy, The University of Faisalabad, Faisalabad, Pakistan
Farah Sattar Nishtar Medical College and Hospital, Multan, Pakistan
Amina` Habib College of Pharmacy, The University of Faisalabad, Faisalabad, Pakistan
Saif`` Babar Combined Military Hospital, Medical and Dental College, Lahore, Pakistan
Abdul Qader Department of Pharmaceutical Chemistry, Government College University Faisalabad, Faisalabad, Pakistan/Department of Primary and Secondary Health Care, Government of Punjab, Pakistan
Mariam Davis Department of Pharmacology, Government College University Faisalabad, Faisalabad, Pakistan
Sana`` Javed` College of Pharmacy, The University of Faisalabad, Faisalabad, Pakistan
Muhammad Usama Ibrahim Khan Department of Primary and Secondary Health Care, Government of Punjab, Pakistan/Department of Drug Inspection, Government of Punjab, Pakistan
Muhammad Haris Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium
Hamza Tariq Department of Pharmacy, Lyallpur Institute of Advanced Studies, Faisalabad, Pakistan
. Afnan Department of Pharmacology, Government College University Faisalabad, Faisalabad, Pakistan

DOI:

https://doi.org/10.54393/pjhs.v4i11.825

Keywords:

Cefixime Trihydrate, Chlorphenaramine Mleate, CCM Gels, Permeation Parameters

Abstract

Cefixime is an antibiotic drug used to treat infection. Chlorphenamine, also known as chlorpheniramine, is an antihistamine and used to treat allergic diseases such urticarial infections and rhinitis Objective: To formulate a gel by using propylene glycol (PG) along with Polyethylene glycol (PEG) in order to enhance the percutaneous absorption and release of cefixime trihydrate and chlorpheniramine maleate from TDDS (transdermal drug delivery system). Methods: Various formulations (G₁ to G₁₃) containing cefixime trihydrate and chlorpheniramine maleate gels (CCM gels) were prepared for this purpose with PG and PEG in different ratios. Firstly, gel optimization was estimated from the physical properties of the gels. Later, the diffusion process was carried out through Franz diffusion cells to find out the permeation kinetic parameters of these gel formulations. Only two of the gels (G₁ and G₃) were selected for further process while the rest were not employed due to stability issues. Results: The obtained results were analyzed by using statistical RSM (response surface methodology) and the link between the independent and response variables was depicted using contour plots. The result of the current study of both these gels indicated high values of flux and ER (enhancement ratio) while a reduction in t_lagvalue. However, no significant difference was seen in the values I/R (input ratio) and K_p(permeation constant) with other formulated gels. Conclusions: It was concluded that the addition of PG and PEG into gels could enhance the permeation of cifixime trihydrate and chlorphenaramine mleate across membrane.

References

Alfei S and Zuccari G. Recommendations to Synthetize Old and New β-Lactamases Inhibitors: A Review to Encourage Further Production. Pharmaceuticals. 2022 Mar; 15(3): 384. doi: 10.3390/ph15030384. DOI: https://doi.org/10.3390/ph15030384

Erkoçoğlu M, Kaya A, Civelek E, Özcan C, Çakır B, Akan A, et al. Prevalence of confirmed immediate type drug hypersensitivity reactions among school children. Pediatric Allergy and Immunology. 2013 Mar; 24(2): 160-7. doi: 10.1111/pai.12047. DOI: https://doi.org/10.1111/pai.12047

Sabbagh F and Kim BS. Recent advances in polymeric transdermal drug delivery systems. Journal of Controlled Release. 2022 Jan; 341: 132-46. doi: 10.1016/j.jconrel.2021.11.025. DOI: https://doi.org/10.1016/j.jconrel.2021.11.025

Hussain Z, Thu HE, Rawas-Qalaji M, Naseem M, Khan S, Sohail M. Recent developments and advanced strategies for promoting burn wound healing. Journal of Drug Delivery Science and Technology. 2022 Feb; 68: 103092. doi: 10.1016/j.jddst.2022.103092. DOI: https://doi.org/10.1016/j.jddst.2022.103092

Szebeni J, Baranyi L, Savay S, Milosevits J, Bunger R, Laverman P, et al. Role of complement activation in hypersensitivity reactions to doxil and hynic PEG liposomes: experimental and clinical studies. Journal of Liposome Research. 2002 Jan; 12(1-2): 165-72. doi: 10.1081/LPR-120004790. DOI: https://doi.org/10.1081/LPR-120004790

Parhi R and Panchamukhi T. RSM-based design and optimization of transdermal film of ondansetron HCl. Journal of Pharmaceutical Innovation. 2020 Mar; 15: 94-109. doi: 10.1007/s12247-019-09373-9. DOI: https://doi.org/10.1007/s12247-019-09373-9

Shahzad Y, Afreen U, Nisar Hussain Shah S, Hussain T. Applying response surface methodology to optimize nimesulide permeation from topical formulation. Pharmaceutical Development and Technology. 2013 Dec; 18(6): 1391-8. doi: 10.3109/10837450.2012.723721. DOI: https://doi.org/10.3109/10837450.2012.723721

Riaz R. Microsponges as Promising Vehicle for Delivery of Antibiotic and Antihistamine for Infectious and Allergic Disorders: Preparation, Characterization and Applications (Doctoral dissertation, Bahauddin Zakariya University Multan). 2019. Available at: http://142.54.178.187:9060/xmlui/handle/123456789/4527.

Turner D, Levine A, Escher JC, Griffiths AM, Russell RK, Dignass A, et al. Management of pediatric ulcerative colitis: joint ECCO and ESPGHAN evidence-based consensus guidelines. Journal of Pediatric Gastroenterology and Nutrition. 2012 Sep; 55(3): 340-61. doi: 10.1097/MPG.0b013e3182662233. DOI: https://doi.org/10.1097/MPG.0b013e3182662233

Katari O and Jain S. Solid lipid nanoparticles and nanostructured lipid carrier-based nanotherapeutics for the treatment of psoriasis. Expert Opinion on Drug Delivery. 2021 Dec; 18(12): 1857-72. doi: 10.1080/17425247.2021.2011857. DOI: https://doi.org/10.1080/17425247.2021.2011857

Baabur-Cohen H, Vossen LI, Krüger HR, Eldar-Boock A, Yeini E, Landa-Rouben N, et al. In vivo comparative study of distinct polymeric architectures bearing a combination of paclitaxel and doxorubicin at a synergistic ratio. Journal of Controlled Release. 2017 Jul; 257: 118-31. doi: 0.1016/j.jconrel.2016.06.037. DOI: https://doi.org/10.1016/j.jconrel.2016.06.037

Suksaeree J, Simchareon W, Pichayakorn W. Effect of glycols permeation enhancer on the release and permeation of meloxicam-natural rubber film through pig skin. Journal of Drug Delivery Science and Technology. 2021 Dec; 66: 102874. DOI: https://doi.org/10.1016/j.jddst.2021.102874

Kis N, Gunnarsson M, Berkó S, Sparr E. The effects of glycols on molecular mobility, structure, and permeability in stratum corneum. Journal of Controlled Release. 2022 Mar; 343: 755-64. doi: 10.1016/j.jconrel.2022.02.007. DOI: https://doi.org/10.1016/j.jconrel.2022.02.007

Chatterjee B, Reddy A, Santra M, Khamanga S. Amorphization of drugs for transdermal delivery-a recent update. Pharmaceutics. 2022 May; 14(5): 983. doi: 10.3390/pharmaceutics14050983. DOI: https://doi.org/10.3390/pharmaceutics14050983

World Health Organization. Restrictions in use and availability of pharmaceuticals, 2010-2018. 2020. [Last cited: 14th Nov 2023]. Available at: https://www.who.int/publications/i/item/9789240014770.

Breindl A, Beck B, Clark T, Glen RC. Prediction of the n-octanol/water partition coefficient, logP, using a combination of semiempirical MO-calculations and a neural network. Molecular Modeling Annual. 1997 Mar; 3: 142-55. doi: 10.1007/s008940050027. DOI: https://doi.org/10.1007/s008940050027

Jiang Z, Qu J, Tian X, Huo X, Zhang J, Guo X, et al. Sol‐gel technique for the preparation of β‐cyclodextrin gold nanoparticles as chiral stationary phase in open‐tubular capillary electrochromatography. Journal of Separation Science. 2019 May; 42(10): 1948-54. doi: 10.1002/jssc.201900071. DOI: https://doi.org/10.1002/jssc.201900071

Das SK, Bedar A, Kannan A, Jasuja K. Aqueous dispersions of few-layer-thick chemically modified magnesium diboride nanosheets by ultrasonication assisted exfoliation. Scientific Reports. 2015 Jun; 5(1): 10522. doi: 10.1038/srep10522. DOI: https://doi.org/10.1038/srep10522

Ioele G, Grande F, De Luca M, Occhiuzzi MA, Garofalo A, Ragno G. Photodegradation of anti-inflammatory drugs: Stability tests and lipid nanocarriers for their photoprotection. Molecules. 2021 Oct; 26(19): 5989. doi: 10.3390/molecules26195989. DOI: https://doi.org/10.3390/molecules26195989

Khan MZ, Makreski P, Murtaza G. Preparation, optimization, in vitro evaluation and ex vivo permeation studies of finasteride loaded gel formulations prepared by using response surface methodology. Current Drug Delivery. 2018 Nov; 15(9): 1312-22. doi: 10.2174/1567201815666180502165436 . DOI: https://doi.org/10.2174/1567201815666180502165436

da Silva Júnior WF, de Oliveira Pinheiro JG, Moreira CD, de Souza FJ, de Lima ÁA. Alternative technologies to improve solubility and stability of poorly water-soluble drugs. Multifunctional Systems for Combined Delivery, Biosensing and Diagnostics. 2017 Jan: 281-305. doi: 10.1016/B978-0-323-52725-5.00015-0. DOI: https://doi.org/10.1016/B978-0-323-52725-5.00015-0