The pharmaceutical industry has to tackle the explosion of high amounts of poorly soluble APIs. This phenomenon leads to numerous sophisticated solutions. These include the use of multifactorial data analysis identifying correlations between the components and dosage form properties, laboratory and production process parameters with respect to the API liberation Example of such API is bicalutamide. Improved liberation is achieved by particle size reduction. Laboratory batches, with different PSD of API, were filled into gelatinous capsules and consequently granulated for tablet compression. Comparative dissolution profiles with Casodex 150 mg (Astra Zeneca) were performed. The component analysis was used for the statistical evaluation of f1 and f2 factors and D(v,0.9) and D[4,3] parameters of PSD to identify optimal PSD values. Suitable PSD limits for API were statistically confirmed in laboratory and in commercial scale with respect to optimized tablet properties. The tablets were bioequivalent with originator (n = 20; 90% CI for ln AUC0-120: 99.8-111.9%; 90% CI for ln cmax: 101.1-112.9%). In conclusion, the micronisation of the API is still an efficient and inexpensive method improving the bioavailability, although there are more complicated and expensive methods available. Statistical multifactorial methods improved the safety and reproducibility of production.
- MeSH
- anilidy chemická syntéza metabolismus MeSH
- biologická dostupnost MeSH
- chemie farmaceutická metody MeSH
- multivariační analýza MeSH
- nitrily chemická syntéza metabolismus MeSH
- tablety MeSH
- terapeutická ekvivalence MeSH
- tosylové sloučeniny chemická syntéza metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
V rámci této experimentální studie byly připraveny biodegradovatelné mikročástice (MČ) na bázi kopolymeru kyseliny mléčné a glykolové (PLGA) metodou odpaření rozpouštědla z jednoduché emulze o/v. Mikročástice obsahovaly nerozpustné antidepresivum mirtazapin. Příprava mikročástic zahrnovala formulační proměnné, a to obsah polymeru (700, 900 nebo 1200 mg), dichlormethanu (5 nebo 10 ml), a/nebo léčiva (200 nebo 400 nebo 600 mg) a objem vodné fáze emulze (400, 600 nebo 800 ml). U sledovaných parametrů byl pozorován vliv na velikost mikročástic a jejich morfologii, enkapsulační účinnost a disoluční chování. Všechny mikročástice byly úspěšně připraveny a jejich velikost se pohybovala v intervalu 165,34 ± 42,88 až 360,17 ± 121,59 μm. Mikročástice vykazovaly prodloužené uvolňování léčiva (v rámci dní), přičemž u některých z nich byl pozorován vícefázový charakter. Bylo zjištěno, že při použití vyššího počátečního množstvím PLGA byly připraveny větší MČ s delším lag time, a to až 34,3 hodin. Na druhé straně vyšší množství použitého léčiva vedlo ke zkrácení lag time. Snížení objemu vnější fáze a násobně vyšší množství dichlormethanu zpomalilo uvolňování mirtazapinu a snížilo enkapsulační účinnost. Výsledky byly dále potvrzeny vícerozměrnou analýzou dat.
In this experimental study, the biodegradable polylactide-co-glycolide (PLGA) microparticles (MP) loaded with the insoluble antidepressant mirtazapine were prepared by the simple o/w solvent evaporation method. The formation involved intrinsic variables, such as the content of polymer (700, 900 or 1200 mg), dichloromethane (5 or 10 ml) and/or drug (200 or 400 or 600 mg), and the volume of the aqueous emulsion phase (400, 600 or 800 ml). The influence of these parameters on the size and morphology of microparticles, encapsulation efficiency, and drug release behavior was observed. All MP were successfully prepared, and their size ranged between 165.34 ± 42.88 and 360.17 ± 121.59 μm. MP exhibited prolonged drug release (days), and some profiles had multiphasic character. It was found that the samples prepared with a higher initial amount of PLGA were bigger with prolonged lag time up to 34.3 hours. On the other hand, higher drug concentrations reduced the lag time. The external phase volume reduction and multiplication of dichloromethane amount prolonged the mirtazapine release and decreased the encapsulation efficiency. These observations were further confirmed by multivariate data analysis.
- Klíčová slova
- PLGA, metoda odpaření rozpouštědla,
- MeSH
- léky s prodlouženým účinkem MeSH
- lidé MeSH
- mirtazapin * farmakologie MeSH
- nanočástice MeSH
- nanočásticový lékový transportní systém MeSH
- příprava léků MeSH
- Check Tag
- lidé MeSH
The aim of the presented research was the preparation and in vitro and in vivo evaluation of mucoadhesive oral films containing nystatin. Multivariate data analysis was used to evaluate an innovative approach, in which a combination of different mucoadhesive polymers was employed. The purpose of this was to assess the effects of such a combination on non-woven insoluble carmellose textile as a drug-release modifier in the structure of the film. It was observed that the mucoadhesive films prepared using polyethylene oxide were more plastic, showed less mechanical resistance and shorter in vitro residence time in comparison with films containing sodium carmellose. The textile used in films containing sodium carmellose significantly prolonged both in vitro and in vivo residence times in rabbits from 50 ± 4 min until 74 ± 4 min and from 48 ± 6 until 80 ± 4 min, respectively. A higher degree of substitution by the acid carboxymethyl group of the textile resulted in slower nystatin dissolution, longer in vitro and in vivo residence times, and higher tensile strength. Textural parameters tensile strength and tensile deformation in conjunction with linear discriminant analysis were able to distinguish the degree of substitution of the textile due to its impact on the studied parameters.
- MeSH
- adhezivita MeSH
- biologická dostupnost MeSH
- experimenty na zvířatech MeSH
- králíci MeSH
- léčivé přípravky MeSH
- nosiče léků chemie MeSH
- nystatin terapeutické užití MeSH
- orální kandidóza * farmakoterapie prevence a kontrola MeSH
- polymery chemie terapeutické užití MeSH
- systémy cílené aplikace léků MeSH
- techniky in vitro MeSH
- textilie MeSH
- ústní sliznice metabolismus účinky léků MeSH
- Check Tag
- králíci MeSH
- Publikační typ
- práce podpořená grantem MeSH
Infectious stomatitis represents the most common oral cavity ailments. Current therapy is insufficiently effective because of the short residence time of topical liquid or semisolid medical formulations. An innovative application form based on bioadhesive polymers featuring prolonged residence time on the oral mucosa may be a solution to this challenge. This formulation consists of a mucoadhesive oral film with incorporated nanocomposite biomaterial that is able to release the drug directly at the target area. This study describes the unique approach of preparing mucoadhesive oral films from carmellose with incorporating a nanotechnologically modified clay mineral intercalated with chlorhexidine. The multivariate data analysis was employed to evaluate the influence of the formulation and process variables on the properties of the medical preparation. This evaluation was complemented by testing the antimicrobial and antimycotic activity of prepared films with the aim of finding the most suitable composition for clinical application. Generally, the best results were obtained with sample containing 20 mg of chlorhexidine diacetate carried by vermiculite, with carmellose in the form of nonwoven textile in its structure. In addition to its promising physicomechanical, chemical, and mucoadhesive properties, the formulation inhibited the growth of Staphylococcus and Candida; the effect was prolonged for tens of hours.
- MeSH
- antiinfekční látky aplikace a dávkování chemie MeSH
- biokompatibilní materiály aplikace a dávkování chemie MeSH
- chemie farmaceutická MeSH
- chitosan chemie MeSH
- chlorhexidin aplikace a dávkování chemie MeSH
- lidé MeSH
- nanokompozity aplikace a dávkování chemie MeSH
- polymery aplikace a dávkování chemie MeSH
- sodná sůl karboxymethylcelulosy aplikace a dávkování chemie MeSH
- stomatitida farmakoterapie mikrobiologie MeSH
- systémy cílené aplikace léků * MeSH
- ústa účinky léků mikrobiologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Texture analysis as a versatile tool for testing the inner structure of materials have been widely used. Though being also used in pharmaceutical industry, it has not been included in standard procedures for evaluation of drug dosage forms. The aim of this study is to measure the thickness of gel layer using texture analysis for the prediction of dissolution profile of very soluble drugs based on hydrophilic and hydrophilic-lipophilic matrix tablets. For the evaluation of the correlation between the thickness of the gel layer as an independent variable and the amount of a released drug as a dependent variable at given time intervals, the multivariate method of partial least squares – PLS-2 regression was used. For the prediction of dissolution characteristics of matrix tablets, a PLS-2 model validated by full cross-validation was developed. A PLS-2 model validated by full cross-validation was developed.
Oral mucosa is an attractive region for the local and systemic application of many drugs. Oral mucoadhesive films are preferred for their prolonged time of residence, the improved bioavailability of the drug they contain, their painless application, their protection against lesions, and their nonirritating properties. This work was focused on preparation of nonmedicated carmellose-based films using both solvent casting and impregnation methods, respectively. Moreover, a modern approach to evaluation of mucoadhesive films applying analysis of texture and subsequent multivariate data analysis was used. In this experiment, puncture strength strongly correlated with tensile strength and could be used to obtain necessary information about the mechanical film characteristics in films prepared using both methods. Puncture work and tensile work were not correlated in films prepared using the solvent casting method, as increasing the amount of glycerol led to an increase in the puncture work in thinner films. All measured texture parameters in films prepared by impregnation were significantly smaller compared to films prepared by solvent casting. Moreover, a relationship between the amount of glycerol and film thickness was observed, and a greater recalculated tensile/puncture strength was needed for an increased thickness in films prepared by impregnation.
The article describes the development of calibration procedures for quantitative evaluation of powder blends utilizing non-contact probe of Raman spectrometer. Two model blends containing ascorbic acid and lactose were chosen. They differed in the used sieve fractions. A new procedure combining convective-diffusive and shear mixing was used for the development of PLS (partial least squares regression) calibration methods. This procedure significantly improves the homogeneity of the mixtures containing fine particles of the size below 100 ??????m. The newly developed methods were further utilized to study blending and the impact of vibrations on the powder blend. The results imply that the particles size has a statistically significant impact on the change of homogeneity in the course of vibration action. The results demonstrated the potential of Raman spectroscopy to be used as a PAT (process analytical technology) method in pharmaceutical analysis.
