IN-SITU FILM-FORMING SOLUTION FOR TOPICAL APPLICATION OF TERBINAFINE HCL: BIOPHARMACEUTICAL EVALUATION AND IN VIVO ANTIFUNGAL PERFORMANCE USING ANIMAL MODEL

Objective: The main purpose of this study is to develop a film-forming solution with optimum physical-mechanical characteristics and excellent antifungal activity to enhance deposition and penetration into the stratum corneum (SC). Methods: The film-forming solutions of terbinafine HCl were formulated using methacrylate copolymers, polyethylene glycol 400, and ethanol as diluent. The selected formulations were subjected to test of physical-mechanical properties, drug release, drug permeation across the stratum corneum and drug deposition study. The best formulation was further evaluated for in vivo antifungal efficacy. Results: The selected formulations exhibited superior pharmaceutical characteristics, including rapid drying, non-stickiness, and being transparency on the skin. Formulation A (FA) had significantly lower tensile strength (4.78 N/m2, p<0.05) and higher percentage elongation at break (33.61%, p<0.05), which reduced the firmness of the film, allowing it to be super-flexible in following the movement of the skin and preventing loss of film through abrasion. FA showed significantly (p<0.05) rapid drug permeation (1510.51 µg/cm2) across the stratum corneum (SC) at 24 h when compared with the other formulations and the positive control proprietary drug (PD), Terbex® cream formulation (475.8 µg/cm2). Conclusion: Having superior physical-mechanical and drug permeation characteristics, FA can be considered as an efficient, reproducible, and efficacious antifungal formulation for topical application.

DEVELOPMENT AND IN VITRO EVALUATION OF PHYTOSOME OF TERBINAFINE HYDROCHLORIDE FOR ORAL DRUG DELIVERY

Objective: The purpose of this study was to develop and in vitro evaluation phytosome of terbinafine HCL to enhance the bioavailability for oral route. Methods: The novel phytosome of terbinafine hydrochloride (TFH) was formulated with the molar ratio (1:2) of drug and phospholipid by using solvent evaporation technique. The resulting TFH-PC was determined by means of particle size analyzer (PSA), percentage yield, microscopy, drug content, transmission electron microscopy (TEM). Substantial contact of terbinafine HCL with phospholipids was completed through Fourier transforms infrared spectroscopy (FTIR). Results: The all relevant results of TFH-PC were showed that the percentage entrapment efficiency of formulation was found in 76% to 90%. In vitro release data were exhibited approximately 65% to 79% of the drug released from the TFH-PC formulation by using dialysis membrane technique. Therefore, Formulation (F3) was accomplished that phytosome contain the superior physical characters and compatibility with drug and phospholipids than to make it easy to overcome the competence of drug to pass the lipid-rich bio-membrane. Conclusion: In present work, terbinafine loaded phytosome was formulated for increasing the oral bioavailability of selected drug. Hence, TER-HCL phytosome were effectively improved the absorption of drug in form of phospholipids complex.

FORMULATION AND OPTIMIZATION OF TERBINAFINE HCl SOLID LIPID NANOPARTICLES FOR TOPICAL ANTIFUNGAL ACTIVITY

Objective: Solid lipid nanoparticles (SLNs) are at the forefront of the rapidly developing field of nanotechnology with several potential applications in drug delivery and research. The aim of this study was to develop and characterize SLNs formulae of Terbinafine HCl (TFH) for topical drug delivery applications. Methods: SLNs were prepared using the solvent injection technique. Glyceryl Monostearate (GMS) served as the lipid base. Three stabilizers; Tween 80, Cremophor RH40, and Poloxamer 188, were used. The effect of stabilizer type and concentration, as well as the lipid concentration, were studied, factorial design of 32*21was applied. The prepared SLNs were characterized regarding their particle size, zeta potential, polydispersity index (PDI), entrapment efficiency percent (EE %), and physicochemical stability. The selected formulae were subjected to further investigations such as morphological studies, in vitro release studies, and Infrared (IR) spectroscopy. They were compared with the marketed cream Lamifen® in term of their antifungal activity against Candida albicans. Results: Lipid concentration, together with the type and concentration of stabilizer, appeared to be the main cornerstones which affect the formation of SLNs. Smaller particle size was observed when increasing the stabilizer concentration and decreasing the lipid concentration. Higher EE% was observed when increasing both the stabilizer and the lipid concentrations. Formulae (F6, F12 andF19) were selected as the most suitable SLNs with optimum particle size of 480.2±18.89, 458.6±12.45 and 246.7±10.5 nm, respectively as well as the highest EE% of 87.13±0.19, 93.69±0.7 and 95.06±0.25, respectively. In vitro microbiological screening of their antifungal activity showed significantly larger zones of inhibition of diameters 25.9±0.25, 25±0.35 and 24.67±0.36 mm, respectively in comparison with the marketed Lamifen® cream which showed a zone of 11.2±0.44 mm diameter. Conclusion: Applying SLNs containing TFH as topical antifungal preparations may be considered as a very promising option as they show good physicochemical characterization with high antifungal activity, which delineates them as a promising dosage form for topical antifungal treatment.

KERION CELSI YANG DISEBABKAN OLEH TRICOPHYTON VERRUCOSUM PADA PASIEN IMUNOKOMPROMAIS

Kerion celsi merupakan manifestasi inflamasi pada infeksi dermatofita zoofilik diskalp. Salah satu penyebabnya adalah Trichophyton verrucosum. Imunitas seluler pada pasien imunokompromais terganggu sehingga rentan terinfeksi dermatofita.Pria, 73 tahun mengeluh benjolan bernanah di kepala yang nyeri dan gatal sejak 3 bulan sebelum konsultasi. Pada pemeriksaan dermatologis parietal skalp didapatkan alopesia berbatas tegas dengan boggy eritematosa 5 cm dan pustul folikular. Pemeriksaan dengan lampu Wood tidak menunjukkan fluoresensi. Pemeriksaan mikroskopik dengan KOH 20% didapatkan hifa dan artrokonidia ektotriks. Numerical rating score (NRS) nyeri 8, dan gatal 4. Identifikasi kultur kerokan kulit kepala dan rambut menunjukkan Trichophyton verrucosum. Pasien didiagnosis kerion celsi ,diterapi dengan griseofulvin microsized 20 mg/kg berat badan/hari selama 8 minggu, dan prednison 0,5 mg/kg berat badan/hari selama 10 hari yang kemudian diturunkan perlahan. Ditambahkan krim terbinafine HCL 1 % didahului kompres basah dua kali sehari. Setelah 8 minggu, perbaikan NRS mencapai nol, tanpa efek samping.Kerion celsi seringkali terjadi pada anak, jarang pada dewasa. Pada kasus ini terjadi pada pasien neoplasma berusia lanjut dalam kemoterapi. Usia lanjut, kanker paru, kemoterapi geftinib, diabetes mellitus dan kontak langsung dengan hewan peliharaan merupakan faktor risiko kondisi imunokompromais dan inokulasi patogen sehingga mempermudah dermatofita menginvasi rambut.Kata kunci: kerion celsi, Tricophyton verrucosum, imunokompromais, griseofulvin

STABILITY-INDICATING METHOD DEVELOPMENT AND VALIDATION OF ITRACONAZOLE AND TERBINAFINE HCL IN BULK AND PHARMACEUTICAL TABLET DOSAGE FORM

Objective: The objective of the present work was to develop and validate the stability-indicating method for the simultaneous estimation of itraconazole and terbinafine HCl in bulk and pharmaceutical tablet dosage form by reversed-phase high-performance liquid chromatography (HPLC). This combination of drugs is not reported for simultaneous HPLC analysis as of now. Methods: The analysis of the developed method was carried on Shimadzu LC Prominence-i 2030 model with Lab Solution software and the separation was done on Shim-pack C18 GIST (250 mm×50 mm, 5 μm) column with a flow rate of 1.2 ml/min and run time of 12 min. The injection volume was 10 μl and mobile phase consisted of acetonitrile and 0.1% triethylamine in the ratio of 90:10 and 225 nm was used as a detection wavelength. Results: The retention time was found to be 3.464 min and 8.705 min for itraconazole and terbinafine HCl, respectively. The calibration curve was found to be linear and r2 values were 0.9989 and 0.9995 for itraconazole and terbinafine HCl, respectively. Conclusion: The stability-indicating method was developed by subjecting itraconazole and terbinafine HCl marketed formulation to various stress conditions such as acidic, basic, oxidative, thermal, and water hydrolysis degradation conditions and the degraded product peaks were well resolved from sample peaks.