Drug depot systems have traditionally relied on the spontaneous dissolution and diffusion of drugs or prodrugs from a reservoir with constant exposure to the surrounding physiological fluids. While this is appropriate for clinical scenarios that require constant plasma concentration of the drug over time, there are also situations where multiple bursts of the drug at well-defined time intervals are preferred. This work presents a drug depot system that enables repeated on-demand release of antibiotics in precise doses, controlled by an external radiofrequency magnetic field. The remotely controlled depot system consists of composite microcapsules with a core-shell structure. The core contains micronized drug particles embedded in a low-melting hydrophobic matrix. The shell is formed by a hydrogel with immobilised magnetic nanoparticles that facilitate local heat dissipation after exposure to a radiofrequency magnetic field. When the melting point of the core material is locally exceeded, the embedded drug particles are mobilised and their surface is exposed to the external aqueous phase. It is shown that drug release can be controlled in an on/off manner by a chosen sequence and duration of radiofrequency pulses. The capacity of the depot system is shown to be significantly higher than that of purely diffusion-controlled systems containing a pre-dissolved drug. The functionality of the depot system is demonstrated in vitro for the specific case of norfloxacin acting on E. coli.
- MeSH
- Anti-Bacterial Agents * MeSH
- Escherichia coli MeSH
- Hydrogels chemistry MeSH
- Nanoparticles * chemistry MeSH
- Drug Liberation MeSH
- Publication type
- Journal Article MeSH
To provide the bilateral advantages of emulsions and hydrogels, a facile approach was used to fabricate nanoemulsions filled hydrogel beads through combining the method of self-emulsification and sodium alginate (SA) ionic gelation. The encapsulation and release behavior of curcumin (Cur) were further investigated. The results indicated that Cur packaged nanoemulsions were with the size of 24.26 ± 0.22 nm. The nanoemulsions filled SA hydrogel beads were spherical shell with the diameter of 0.46 ± 0.02 mm. For Cur, the EE and LC of emulsion filled SA hydrogel beads were 99.15 ± 0.85% and 7.25 ± 3.16 mg/g respectively. The release behavior could be regulated by external pH condition. The release behavior at pH 9.0 displayed a higher release rate than that at pH 7.0. Cur released behavior well followed the Hixcon-Crowell model which indicated that Cur was released in a diffusion-controlled model. Comparatively investigation of microstructure using field emission scanning electron microscope (FE-SEM) further investigates the corrosion behavior of SA gel beads during Cur release. The worth-while endeavor provided a practical combined technique of emulsions and ionic gelation to fabricate hybrid hydrogel beads that have potential in delivery system for hydrophobic composition.
- MeSH
- Alginates chemistry MeSH
- Emulsions MeSH
- Hydrophobic and Hydrophilic Interactions MeSH
- Hydrogels chemistry MeSH
- Kinetics MeSH
- Curcumin chemistry MeSH
- Microspheres * MeSH
- Nanostructures chemistry MeSH
- Drug Carriers chemistry MeSH
- Capsules MeSH
- Drug Liberation * MeSH
- Publication type
- Journal Article MeSH
Unknown impurities were identified in ibuprofen (IBU) soft gelatin capsules (SGCs) during long-term stability testing by a UHPLC method with UV detection and its chemical formula was determined using high resolution/accurate mass (HRAM) LC-MS. Reference standards of the impurities were subsequently synthesized, isolated by semi-preparative HPLC and characterized using HRAM LC-MS, NMR and IR. Two impurities were formed by esterification of IBU with polyethylene glycol (PEG), which is used as a fill of the SGCs, and were identified as IBU-PEG monoester and IBU-PEG diester. Two other degradants arised from reaction of IBU with sorbitol and sorbitan, which are components of the shell and serves as plasticizers. Thus, IBU sorbitol monoester (IBU-sorbitol) and IBU sorbitan monoester (IBU-sorbitan ester) were identified. An UHPLC method was further optimized in order to separate, selectively detect and quantify the degradation products in IBU SGCs.
PURPOSE: The aim of this study was to investigate the suitability of hard capsules of different composition (gelatin-G, gelatin coated with hydroxypropyl cellulose-G/HPC, and hypromellose-H) for a coating with aqueous dispersion of pH-dependent synthetic polymer Eudragit(®) FS (E(FS)) and to evaluate in vitro the coated capsules as transport systems for ileo-colonic drug delivery. METHODS: Three sets of hard capsules with increasing coating levels (5-30%) were obtained by Wurster technique. The release of model drug (caffeine) from prepared samples was tested using paddle dissolution method with continual pH change (pH 1.2-2 h, 6.8-4 h and 7.5-2 h). RESULTS: During the coating process, no problems occurred and similar suitability of capsules materials for E(FS) application was observed in contrast to some published reports. The application of HPC subcoating onto gelatin capsules surface was shown as the redundant step. The samples G/E(FS)10-15% and H/E(FS)15-20% with 6 h lag time and fast drug release after the pH adjustment to 7.5 corresponded with the requirements for ileic drug delivery. Samples releasing the drug after the pH change to 7.5 in 2-h interval such as G/E(FS) 20%, G/HPC/E(FS) 25% and H/E(FS) 25% are considered as promising transport systems to ileo-colonic area. Samples G/E(FS) 25-30%, G/HPC/E(FS) 30% and H/E(FS) 30% with 7 h lag time could be used for colon delivery. CONCLUSION: The desired intestinal part could be targeted without significant formulation changes only by the selection of capsules shell forming material and suitable E(FS) coating thickness.
- MeSH
- Biological Transport MeSH
- Time Factors MeSH
- Ileum metabolism MeSH
- Caffeine pharmacokinetics MeSH
- Colon metabolism MeSH
- Hydrogen-Ion Concentration MeSH
- Polymethacrylic Acids chemistry MeSH
- Drug Delivery Systems methods MeSH
- Delayed-Action Preparations MeSH
- Humans MeSH
- Methylcellulose analogs & derivatives chemistry MeSH
- Solubility MeSH
- Capsules chemistry MeSH
- Gelatin chemistry MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Výroba měkkých želatinových tobolek je jednocyklový výrobní proces závislý na kvalitě želatinové hmoty a vlastnostech náplně. Tobolky jsou citlivé na vlhkost vzduchu a vyžadují dodržení stanovení teploty při výrobě a skladování. Vlhkost (voda) může migrovat do stěny, případně až do náplně tobolek, a ovlivnit tak jakost a stabilitu vyrobených tobolek. Kvalitu tobolek ovlivňují také složení želatinové hmoty, složení náplně a migrace složek náplně do stěny. Tato experimentální práce se věnuje vlivu viskozity želatinové hmoty, tloušťky želatinových pásů a zvoleného způsobu sušení tobolek na migraci vody ze stěny do náplně tobolek. V souvislosti s uvedenými faktory se sleduje také vzhled náplně tobolek.
Manufacture of soft gelatine capsules in a one-cycle manufacturing process dependent on the quality of gelatine mass and the properties of the filling. Capsules are sensitive to aerial moisture and require observance of the temperature prescribed for their manufacture and storing. Moisture (water) can migrate into the shell, or into the filling of capsules and thus affect both the quality and stabihty of the capsules produced. The quality of capsules is also influenced by the composition of gelatine mass, composition of the filling, and migration of the components of the filing into the shell. The present experimental paper is devoted to the effect of viscosity of gelatine mass, thickness of gelatine ribbons, and the selected method of drying of capsules on the migration of water from the shell into the filling of capsules. The appearance of the filling of capsules in connection with the above-stated factors is also examined.
Měkké želatinové tobolky jsou lékovou formou vhodnou zejména pro aplikaci citlivých a technologickyproblémových léčiv, maskují nepříjemnou chuť nebo zápach léčiva, barevné kombinace zvyšujíbezpečnost terapie vyloučením záměn. Jejich výroba je náročná, závisí na kvalitě želatiny a želatinovéhmoty pro stěnu tobolek, na vlastnostech náplně, na vzájemných interakcích mezi náplnía stěnou a na speciálním „know-how“, které je bezpodmínečným předpokladem úspěšné výroby tétolékové formy. Vysoké výrobní náklady vedou ze strany výrobců k maximální racionalizaci všechvýrobních kroků. Článek je přehledem charakterizujícím měkké želatinové tobolky, jejich výrobnípostupy a hodnocení jakosti.
Soft gelatin capsules are a dosage form suitable particularly for administration of sensitive drugsposing technological problems. They mask an unpleasant taste or smell of the drug and the colourcombinations increase the safety of therapy by excluding interchangings. Their manufacture isundemanding, it depends on the quality of gelatin and the gelatin mass for the shell of the capsules,on the properties of the fill, on mutual interactions between the fill and the shell, and on a specialknow-how, which is an unconditional precondition of successful manufacture of this dosage formThe paper is a review characterizing soft gelatin capsules, processes of their manufactures, andquality evaluation.
- MeSH
- Capsules administration & dosage therapeutic use MeSH
- Gelatin administration & dosage therapeutic use MeSH
- Publication type
- Review MeSH
