Study of base influence on the active pharmaceutical ingredients releasing from combined ointments with antimycotic action
DOI:
https://doi.org/10.14739/2409-2932.2018.1.123687Keywords:
2-mercaptobenztiazol, chinozol, oinment, tinea pedis, ointment basesAbstract
Questions of mycotic diseases therapy keep staying in focus of clinical dermatology interest that is caused first of all by their considerable prevalence for international population. At the same time the dominating pathologies in this area are foot mycosis including skin, foot web space and nail plate affections.
Etiotropic pharmacotherapy of foot skin and web spaces is carried out using topical antifungal medications effective against dermatomycetes. Also taking into account the frequent mixt infections, medicines with antibacterial action are desirable. Also topical antifungal medicines for therapy of foot skin mycosis have to satisfy the next requirements as rapid absorbance, safety and usability besides efficacy. Domestic dermatology for these aims has a great pharmacotherapeutical arsenal proposed by 34 semisolid dosage forms, 15 from them are made in Ukraine and the remainder are imported in our country. At the heart of practically all antimycotic medicines for topical therapy of smooth foot skin (as imported so domestic) imidazole and triazole derivatives are used and because of their high value they limit the therapeutical potential of population with low profit.
2-mercaptobenzothiazole is interesting as biologically active component of ointments not only because of broad spectrum of antifungal and antibacterial action but also exceptional hydrophobic characteristics which provide long adhesion even after washing during hygienic procedures.
In this connection creating of semisolid dosage forms for the topical treatment of skin integument and interdigital folds with biologically active substances from the group of nonspecific antifungal matters (2-mercaptobenzothiazole, chinosolum) on the base of domestic technologies is actual for modern pharmaceutical and medical science.
During creating of semisolid dosage forms for the external use one of the main experimental fragments is a selection of base which provides high consumer characteristics of medicine and its efficacy.
The aim of this work is biopharmaceutical validation of rational composition of semisolid dosage form for external use containing the combination of 2-mercaptobenzothiazole and chinosolum.
Materials and methods. As a delivery vehicle for developing pharmacotherapeutical medicine the bases widely used in manufacturing of semisolid dosage forms, providing easy “wipe-off" effect after application, non-allergic and non-sensibilic after tracing, available for national producer and described in literature were studied.
As the active pharmaceutical ingredients for antimycotic ointment 2-mercaptobenzothiazole and chinosolum in concentration 1% and 1% accordingly providing with suitable level of antifungal activity were used.
Taking into account the advisability of high dispersion degree of medical substances in semisolid dosage forms for external use and physical-chemical properties of active pharmaceutical ingredients 2-mercaptobenzothiazole was added in all bases after preliminary dissolution in polyethylenoxyde 400 with heating and chinosolum was added after dissolution in prescribed or minimal amount of water.
2-mercaptobenzothiazole and chinosolum releasing from ointment compositions was studied with equilibrium dialysis method by Kruvchinsky at the temperature 32±0,5˚С through the semipermeable film “Kuprofan” in the Franz cell apparatus (producer PermeGear, Inc., USA).
As a dialysis medium taking into account 2-mercaptobenzothiazole solubility we used solution containing methanol and water 1:1 and chinosolum releasing was carried out into water. Concentration of active pharmaceutical substances released from experimental ointments after 30 min was determined by spectrophotometric method.
Results. The obtained results indicate significant advantage of the hydrophilic ointment bases, which provide an optimal level of release of 2-mercaptobenzothiazole and chinosolum from the experimental composite soft dosage forms for external use. Based on the obtained data, ointment compositions with 2-mercaptobenzothiazole and chinosolum on the basis of sodium carboxymethylcellulose (prescription №1) and methylcellulose (prescription №2) glycerogel were selected for further research.
Conclusions. It was established that the sort of base significantly influences on 2-mercaptobenzothiazole and chinosolum releasing from the antimycotic formulations of semisolid dosage forms for external use.
Variance analysis of results revealed that delivery vehicles on the base of sodium carboxymethylcellulose and methylcellulose glycerogel provide optimal 2-mercaptobenzothiazole and chinosolum releasing.
References
Sokolova, T. V., Malyarchuk, T. A., & Gazaryan, O. L. (2014) Mikozy stop – e'pidemiologicheskaya problema dermatologii [Mycosiss feet is an epidemiology problem of dermatology]. Russkij medicinskij zhurnal, 22(8), 571–577. [in Russian].
Sokolova, T. V., Maliarchuk, A. P., & Maliarchuk, T. A. (2013) Rezul'taty mnogocentrovogo issledovaniya po izucheniyu poverkhnostnykh mikozov kozhi v regionakh Rossijskoj Federacii i ocenke e'ffektivnosti ikh lecheniya sertakonazolom [Results of a multicenter trial to investigate the incidence of superficial mycoses in the regions of the Russian Federation and to evaluate the efficiency of their treatment with sertaconazole]. Klinicheskaya dermatologiya i venerologiya, 11(5), 28–39. [in Russian].
Fedotov, V. P. (2012) Aktual'nye problemy kandidoza [Issues of the day of candidiasis]. Dermatologiya. Kosmetologiya. Seksopatologiya, 1/4(12), 103–128. [in Russian].
Yakovlev, A. B. (2012) E'pidermal'nye mikozy kozhi v praktike dermatologa [Epidermal mycosiss of skin are in practice of dermatologist]. Lechashij vrach, 5, 53–55. [in Russian].
Yarnykh, T. G., & Garkavtseva, O. A. (2012) Analiz assortimenta mazevyh osnov [Analysis of assortment of ointments’ bases]. Nauchnye vedomosti Belgorodskogo gosudarstvennogo universiteta. Seriya Medicina. Farmaciya, 18, 10-3(129), 16–22. [in Russian].
Gladyshev V.V., Gnitko I.V., Lisianskaia A.P., Diudiun A.D. (2014) Izuchenie intensivnosti vysvobozhdeniya minoksidila iz mazevykh osnov [Study of intensity of freeing of мynoxydil from ointments bases]. Nauchnye vedomosti Belgorodskogo gosudarstvennogo universiteta. Seriya Medicina. Farmaciya, 28, 24(195), 242–245. [in Russian].
Luts, V. V., Kolycheva, I. L., Hladyshev, V. V., & Lisianska, A. P. (2017) Obgruntuvannia optymalnykh kontsentratsii aktyvnykh farmatsevtychnykh inhrediientiv u kombinovanykh m’iakykh likarskykh formakh dlia zovnishnoho zastosuvannia antymikotychnoi dii [Basis of optimal concentration of active pharmaceutical ingredients in combdrugs for external use with antimycotic activity]. Farmatsevtichnyi zhurnal, 3–4, 53–59. [in Ukrainian].
Hroshovyi, T. A., Martseniuk, V. P., Kucherenko, L. I., & Vronska, L. P. (2008) Matematychne planuvannia eksperymentu pry provedenni naukovykh doslidzhen v farmatsii [The mathematical planning of experiment is during realization of scientific researches in pharmacya]. Ternopil: TDMU. [in Ukrainian].
Romanina, D. M., Berdey, I. I., Gladishev, V. V., & Lisyanska, A. P. (2016) Vyvchennia vplyvu osnov-nosiiv na biofarmatsevtychni vlastyvosti m’iakoi likarskoi formy prazikvantelu dlia zovnishnoho zastosuvannia [Study of ointment base influence over biopharmaceutical characteristics of praziquantel semisolid dosage form for external use]. Farmatsevtychnyi zhurnal, 5, 37–42. [in Ukrainian].
Antipenko, L. N., Luc', V. V., Korzhova, A. S., & Vasyuk, S. A. (2016) Razrabotka i validaciya UF-spektrofotometricheskoj metodiki opredeleniya sul'fata 8-oksikhinolina i 2-merkaptobenzotiazola v lekarstvennoj forme [Development and validation of UV spectrophotometric method of detection of quinolin-8-ol sulfate and 2-mercaptobenzothiazole determination in pharmaceutical dosage form]. Recept, 6, 655–657. [in Russian].
Downloads
How to Cite
Issue
Section
License
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access)
