Microbiological and Analytical Evaluation of Semi-Solid Formulations of Doxycycline Hyclate under Accelerated Stability Conditions
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Abstract
Doxycycline Hyclate (DOX) is a broad-spectrum antibiotic that belongs to the tetracycline family. It has been widely used in the treatment of several inflammatory diseases, and is considered the first-line therapy in the management of moderate to severe cases of acne. In this research, Doxycycline was formulated in four semi-solid formulations (F1and F2 as Gels, F3 and F4 as ointments), then these formulations were subjected to accelerated stability conditions for three months. The formulations were evaluated using microbiological and analytical methods after one and three months. Agar well diffusion method was used as a microbiological method to screen the antibacterial activity of semi-solid formulations against two types of bacteria, Staphylococcus Aureus and Pseudomonas Aeruginosa. HPLC was used as an analytical method for the quantitative and qualitative determination of these formulations. A comparison between a microbiological assay and analytical assay was achieved to evaluate the activity. The results showed that the ointment formulations were more stable than gel formulations since the percentages of drug were 91%, 93% at 25 ˚C after one month for formulations (F3, F4) against 90%,65% for formulations (F1, F2) respectively. Antibacterial activity results showed that formulation F4 had the highest zone of inhibition, which is 31mm for S.aurues and 26 mm for P. aeruginosa after storing it for three months at 25C°. The formulations were still effective despite the chemical degradation of doxycycline, this effectiveness returns to the fact that degradation products could still have active structural parts responsible for the antibacterial activity.
Received 02/04/2023
Revised 02/10/2023
Accepted 04/10/2023
Published Online First 20/02/2024
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References
Kashani-Asadi-Jafayeeeri F, Hadjizadeh A. Niosome-encapsulated Doxycycline Hyclate for Potentiation of Acne Therapy: Formulation and Characterization. Pharm Nanotechnol. 2022; 10(1): 56-68. https://doi.org/10.1101/2021.09.28.462256
Aliah A, Oktaviani WW, Erdiana AP, Dwipayanti KS, Utami RN, Permana AD. Enhanced skin localization of doxycycline using microparticles and hydrogel: effect of oleic acid as penetration enhancer. Pharmaciana. 2021; 11(2): 239-250. http://dx.doi.org/10.12928/pharmaciana.v11i2.21044
Patel RS, Parmar M. Doxycyline Hyclate.. In: StatPearls. Treasure Island (FL). National library of medicine. NCBI. StatPearls Publishing; 2023.
Borse VA, Gangude AB, Deore AB. Formulation and evaluation of antibacterial topical gel of doxycycline hyclate, neem oil and tea tree oil. Indian J Pharm Educ Res. 2020; 54(1): 206–212. https://doi.org/10.5530/ijper.54.1.24
KirciK L, Weiss JS, Del Rosso JQ, Stakias V, London A, Keynan R, et al. Formulation and Profile of FMX101 4% Minocycline Topical Foam for the Treatment of Acne Vulgaris. J Clin Aesthet Dermatol. 2020; 13(4): 14–21.
Gugleva V, Titeva S, Rangelov S, Momekova D. Design and in vitro evaluation of doxycycline hyclate niosomes as a potential ocular delivery system. Int J Pharm. 2019;567: 11843.https://doi.org/10.1016/j.ijpharm.2019.06.022
Smith R, Russo J, Fiegel J, Brogden N. Antibiotic delivery strategies to treat skin infections when innate antimicrobial defense fails. Antibiotic. 2020; 9(2): 1-25. https://doi.org/10.3390/antibiotics9020056
Cheng T, Tai Z, Shen M, Li Y, Yu J, Wang J, et al. Advance and Challenges in the Treatment of Skin Diseases with the Transdermal Drug Delivery System. Pharmaceutics. 2023; 15(8):2165. https://doi.org/10.3390/pharmaceutics15082165
Marco AD, Giuffrida R, Bonamonte D, Conforti C, Barlusconi C, Foti C, et al. Topical antibiotics in the dermatological clinical practice: Indications, efficacy, and adverse effects. Dermatol Ther. 2020; 33(6). https://doi.org/10.1111/dth.13824
Montejo O, Modamio P, Lastra CF, Segarra I, Mestorino N, Mariño EL. Twenty-Week Solid-State Stability Study of Combined Doxycycline, Trimethoprim and Sulfamethoxypyridazine Formulations after Extemporaneous Preparation for Veterinary Use. Pak Vet J. 2015; 35(1): 111-113.
González-González O, Ramirez OI, Ramirez BI, O'Connel P, Ballesteros M, Torrado JJ, et al. Drug Stability: ICH versus Accelerated Predictive Stability Studies. Pharmaceutics. 2022; 14(11): 2324. https://doi.org/10.3390/pharmaceutics14112324
Loftin KA, Surampalli R, Adams CD, Meyer MT. Effects of ionic strength, temperature, and pH on degradation of selected antibiotics. J Environ Qual. 2008; 37(2): 378–386. https://doi.org/10.2134/jeq2007.0230
Jutglar M, Foradada M, Caballero F. Hoogmartens J, Adams E, Influence of the solvent system on the stability of doxycycline solutions. J Pharm Biomed Anal. 2018; 159: 60-65.https://doi.org/10.1016/j.jpba.2018.06.054
Li WN, Bao YY, Zhou QX, Degradation pathways and main degradation products of tetracycline antibiotics: research progress. Ying Yong Sheng Tai Xue Bao. 2012; 23(8): 2300-2308.
Gupta NV, Shanmuganathan S, Kanna1 S, Sastr KT. A 23factorial design for formulation and development of doxycycline hydrochloride in situ gel forming solution for wound healing application. Int J App Pharm, 2021; 13(3): 221-232. https://doi.org/10.22159/ijap.2021v13i3.39696
Soni K, Gour V, Agrawal P, Haider T, Bakshi A, Soni V. Carbopol-olive oil-based bigel drug delivery system of doxycycline hyclate for the treatment of acne, Drug Dev Ind Pharm 2021; 47(6): 954-962. https://doi.org/10.1080/03639045.2021.1957916
Javali MA, Vandana KL. A comparative evaluation of atrigel delivery system (10% doxycycline hyclate) Atridox with scaling and root planing and combination therapy in treatment of periodontitis: A clinical study. J Indian Soc Periodontol. 2012; 16(1): 43-8.https://doi.org/10.4103/0972-124x.94603 .
.Fayyadh AA, Essa AF, Batros SS, Shallal ZS. Studying the Crystal Structure, Topography, and Anti-bacterial of a Novel Titania (TiO2 NPs) Prepared by a Sol-gel Manner. Baghdad Sci J. 2019; 16(4): 0910 https://doi.org/10.21123/bsj.2019.16.4.0910
Toma JJ, Aziz FH. Antibacterial Activity of Three Algal Genera against some Pathogenic Bacteria. Baghdad Sci J. 2023; 20(1): 0032.https://doi.org/10.21123/bsj.2022.6818
Meetam P, Limmatvapirat C, Krongrawa W, Limmatvapirat S, Pongnimitprasert N. Formulation and evaluation of gels containing coconut kernel extract for topical application. Asian J Pharm Sci. 2018; 13(5): 415-424. https://doi.org/10.1016/j.ajps.2018.01.005
Salas AL, Uriburu FMC, Zampi C, Arias M. Hydroalcoholic gel with Argentine propolis: the potential for antimicrobial and antioxidant activities, stability evaluation, and in vitro phenolic release. J Apic Res. 2020; 59(5): 735-743. https://doi.org/10.1080/00218839.2020.1790791
Zhong SF, Yang B, Xiong Q, Lan ZG, Ying GG. Hydrolytic transformation mechanism of tetracycline antibiotics: Reaction kinetics, products identification and determination in WWTPs. Ecotoxicol Environ Saf. 2022; 229: 113063. https://doi.org/10.1016/j.ecoenv.2021.113063
Maslii Y, Ruban O, The Influence of pH Values on the Rheological, Textural and Release Properties of Carbomer Polacril® 40P-Based Dental Gel Formulation with Plant-Derived and Synthetic Active Components. Molecules. 2020; 25 (21): 5018. https://doi.org/10.3390/molecules25215018
Hinks ML, Brady MV, Lignell H, Song M, Grayson GW, Bertram AK, et al. Effect of viscosity on photodegradation rates in complex secondary organic aerosol materials. Phys Chem Chem Phys. 2016; 18: 8785-8793. https://doi.org/10.1039/C5CP05226B