Drug loading into mesoporous carriers may help to improve the dissolution of poorly aqueous-soluble drugs. However, both preparation method and carrier properties influence loading efficiency and drug release. Accordingly, this study aimed to compare two preparation methods: formulation into liquisolid systems (LSS) and co-milling for their efficiency in loading the poorly soluble model drug cyclosporine A (CyA) into mesoporous magnesium aluminometasilicate Neusilin® US2 (NEU) or functionalized calcium carbonate (FCC). Scanning electron microscopy was used to visualize the morphology of the samples and evaluate the changes that occurred during the drug loading process. The solid-state characteristics and physical stability of the formulations, prepared at different drug concentrations, were determined using X-ray powder diffraction. In vitro release of the drug was evaluated in biorelevant media simulating intestinal fluid. The obtained results revealed improved drug release profiles of the formulations when compared to the milled (amorphous) CyA alone. The dissolution of CyA from LSS was faster in comparison to the co-milled formulations. Higher drug release was achieved from NEU than FCC formulations presumably due to the higher pore volume and larger surface area of NEU.
- MeSH
- difrakce rentgenového záření MeSH
- pomocné látky * MeSH
- poréznost MeSH
- rozpustnost MeSH
- voda * MeSH
- Publikační typ
- časopisecké články MeSH
A novel ultra-high performance chromatography method with multichannel detection that allows fast, sensitive, and robust analysis of an antifungal drug terbinafine and its three main impurities β-terbinafine, (Z)-terbinafine, and 4-methylterbinafine in just 5.0 min has been developed. Analysis of terbinafine is important in pharmaceutical analysis since it enables the detection of its impurities at very low concentrations. In this study, we focused on the development, optimization, and validation of the UHPLC method as well as its subsequent application in the evaluation of terbinafine and its three main impurities in the dissolution medium to reveal the incorporation of terbinafine in two poly(lactic-co-glycolic acid) (PLGA) carriers and testing of the drug release at pH 5.5. PLGA based drug delivery systems such as solid dispersions, thin films, microparticles, and nanoparticles are new favorable ways of terbinafine administration. PLGA features excellent tissue compatibility, biodegradation, and adjustable drug release profile. Our pre-formulation study indicates that poly(acrylic acid) branched PLGA polyester has more suitable properties than tripentaerythritol branched PLGA polyester. Therefore, the former is likely to enable design of a new drug delivery system for topically applied terbinafine that could facilitate its administration and increase patient compliance.
Although the systemic administration of terbinafine is quite well tolerated, topical treatment of the local infections is often preferred. New formulation strategies in topical antifungal therapy represent the polymeric nanoparticles (NPs). We successfully employed the originally synthesized PLGA derivatives of branched architectures of various molar masses, branching ratio, and high number of terminal hydroxyl or carboxyl groups for compounding of terbinafine loaded nanoparticles by nanoprecipitation method. Employing the polymers with tailored properties allowed us to formulate the NPs with desired particle size, loading capacity for drug, mucoadhesive properties, and drug release profile. The hydrophobicity and the polyester concentration revealed the main impact on the NPs size ranging from 100 to 600 nm. The stability of the nanosuspension is demonstrated by zeta potential >25 mV, and polydispersity index values <0.2. We used terbinafine in its less dissolved form of the base to increase the drug loading and delay the release. Cationic surfactant as stabilizer give the NPs high positive surface charge enhancing the adhesion to the mucosal surfaces. All formulations provided prolonged sustained release of terbinafine for several days. Antimicrobial potential has been proven by agar-well diffusion method.
- MeSH
- antifungální látky aplikace a dávkování chemie MeSH
- aplikace lokální MeSH
- hydrofobní a hydrofilní interakce MeSH
- kationty MeSH
- kopolymer kyseliny glykolové a mléčné chemie MeSH
- nanočástice chemie MeSH
- nosiče léků chemie MeSH
- povrchově aktivní látky chemie MeSH
- povrchové vlastnosti MeSH
- příprava léků metody MeSH
- rozpustnost MeSH
- terbinafin aplikace a dávkování chemie MeSH
- uvolňování léčiv MeSH
- velikost částic MeSH
- viskozita MeSH
- Publikační typ
- časopisecké články MeSH
Determination of urinary retinol, which is a new promising early biomarker of renal damage typically expressed in the clinical environment as retinol/creatinine ratio, is currently difficult to accomplish. We have developed and validated the new ultra-high-performance liquid chromatography method with UV and mass spectrometry detection for the separation and quantification of retinol and creatinine in human urine in a single run. The separation of these two substances with completely different physicochemical properties was achieved using a column packed with fluorinated stationary phase and acetonitrile and aqueous ammonium formate buffer as the mobile phases. The separation was completed within 4 min. Our new method involves very fast and simple sample preparation requiring small amount of sample matrix and solvents. Deuterium labeled internal standard was used for the more precise quantification. The method was tested with real-life samples using urine collected from patients suffering from breast, colorectal, head, and neck cancer.
- MeSH
- biologické markery moč MeSH
- kalibrace MeSH
- kreatinin chemie moč MeSH
- ledviny patofyziologie MeSH
- lidé MeSH
- referenční standardy MeSH
- reprodukovatelnost výsledků MeSH
- rozpouštědla MeSH
- vitamin A chemie moč MeSH
- vysokoúčinná kapalinová chromatografie metody MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Background: Oral liquid solutions of the diuretic active ingredient furosemide (FUR) marketed across Europe do not comply with recent requirements for paediatric preparation owing to their ethanol content and, moreover, in some countries only tablet or injection dosage forms of furosemide are available. Objectives: To formulate extemporaneous paediatric ethanol-free solutions of FUR (2 mg/mL) with suitable solubility in the aqueous vehicle and an acceptable taste and to evaluate their stability under two different storage conditions during a 9-month study period. Methods: Our work presents two developed formulations of FUR ethanol-free paediatric oral solutions 2 mg/mL for easy extemporaneous compounding in a pharmacy. FUR solubility avoiding the use of ethanol was achieved using sodium hydroxide (formulation F1) or disodium hydrogen phosphate dodecahydrate (formulation F2). The preparations were stored at 25°C±3°C or at 40°C±0.5°C and protected from light. For FUR and preservative, methylparaben (MP), a stability assay was conducted by a high-performance liquid chromatography validated method and determination of pH stability. Results: The remaining FUR concentration was >90% of the initial concentration after 270 days in both formulations at both storage conditions, 25°C and 40°C. The concentration of MP decreased significantly in the formulation F2 stored at 40°C. Conclusions: Both formulations were stable when stored at room temperature for up to 9 months; formulation F1 was stable even at 40°C. MP used as an antimicrobial agent fully satisfied the recommended criteria for preservative efficacy in oral preparations according to the European Pharmacopoeia 9.0 (5.1.3).
- Publikační typ
- časopisecké články MeSH
