hard capsules
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Tobolky ETALOCK splňují požadavky kladené na tvrdé želatinové tobolky. Podíl vadných produktůpři jejich formování a plnění se pohybuje v rozmezí 0,7 až 1,5 %. Pokud plnící stroje vyřazují i tobolkybez zřejmých vad, souvisí to s nedokonalým technickým stavem plniček.
The capsules ETALOCK meet the requirements for hard gelatine capsules. The share of defectiveproducts in the process of their forming and filling ranges within 0.7–1.5 %. If the filling machineseliminate also capsules without evident defects, it is due to the imperfect technical conditions of thefilling machines.
V současné době existují v celém v světě miliony lidí závislých na benzodiazepinech. Forma somatické i psychické závislosti znemožňuje okamžité vysazení léčiv. Jedním z dlouhodobě osvědčených léčebných postupů je převedení pacientů na diazepam, který má dlouhý bio-logický poločas. Po stabilizaci následuje postupné snižování dávek až do stavu placeba. Vhodnou lékovou formou se jeví tvrdé želatinové tobolky, ve kterých mohou být kromě diazepamu obsaženy i další adjuvantní léčiva z řady antipsychotik, antidepresiv a betablokátorů, zmírňujících abstinenční příznaky. Vzhledem k nízkým dávkám léčiv musí mít tobolky vyhovující obsahovou stejnoměrnost dle požadavků ČL 2017. V běžné lékárenské praxi se nepodařilo tomuto požadavku vyhovět. Při použití vhodného plniva a běžného kuchyňského mixéru je ale možné požadavek splnit. Výsledkem jsou tobolky s obsahem diazepamu v rozsahu 2,125 až 0,492 mg, určené ke snižování dávky o 15 %. Zvolená technologie zaručí způsobilost procesu, a je tedy schopna produkovat/vyrábět tobolky v rámci tolerovaného rozmezí hodnot pro hmotnostní a obsahovou stejnoměrnost.
At present, millions of people in the world are addicted to benzodiazepines. The form of both somatic and psychic addiction does not permit immedi-ate discontinuation of these drugs. One of methods, which has been used successfully for long time, is to switch the patients to diazepam. Diazepam has long biological half-life and after stabilization, gradual dose reduction until placebo dose is reached can follow. Hard gelatinous capsules seem to be the most suitable dosage forms for this process because they may contain also other drugs alleviating abstinence symptoms – antipsychotics, antidepressants, or beta blockers. Because of low doses of these active substances, the capsules need to meet pharmacopoeial requirements for content uniformity of dosage units. In common pharmacy practice, it is very difficult to meet this requirement. If suitable filler and common kitchen mixer are used, it is possible and diazepam capsules containing 2.125 to 0.492 mg of active substance can be produced, allowing for dose reduction in 15% decrements. This technology guarantees the capability of the process, that is, capsules within required mass and content uniformity limits can be produced/manufactured.
V současné době existují v celém v světě miliony lidí závislých na benzodiazepinech. Forma somatické i psychické závislosti znemožňuje okamžité vysazení léčiv. Jedním z dlouhodobě osvědčených léčebných postupů je převedení pacientů na diazepam, který má dlouhý biologický poločas. Po stabilizaci následuje postupné snižování dávek až do stavu placeba. Vhodnou lékovou formou se jeví tvrdé želatinové tobolky, ve kterých mohou být kromě diazepamu obsaženy i další adjuvantní léčiva z řady antipsychotik, antidepresiv a betablokátorů, zmírňujících abstinenční příznaky. Vzhledem k nízkým dávkám léčiv musí mít tobolky vyhovující obsahovou stejnoměrnost dle požadavků ČL 2017. V běžné lékárenské praxi se nepodařilo tomuto požadavku vyhovět. Při použití vhodného plniva a běžného kuchyňského mixéru je ale možné požadavek splnit. Výsledkem jsou tobolky s obsahem diazepamu v rozsahu 2,125 až 0,492 mg, určené ke snižování dávky o 15 %. Zvolená technologie zaručí způsobilost procesu, a je tedy schopna produkovat/vyrábět tobolky v rámci tolerovaného rozmezí hodnot pro hmotnostní a obsahovou stejnoměrnost.
At present, millions of people in the world are addicted to benzodiazepines. The form of both somatic and psychic addiction does not permit immediatediscontinuation of these drugs. One of methods, which has been used successfully for long time, is to switch the patients to diazepam. Diazepamhas long biological half-life and after stabilization, gradual dose reduction until placebo dose is reached can follow. Hard gelatinous capsules seemto be the most suitable dosage forms for this process because they may contain also other drugs alleviating abstinence symptoms – antipsychotics,antidepressants, or beta blockers. Because of low doses of these active substances, the capsules need to meet pharmacopoeial requirements forcontent uniformity of dosage units. In common pharmacy practice, it is very difficult to meet this requirement. If suitable filler and common kitchenmixer are used, it is possible and diazepam capsules containing 2.125 to 0.492 mg of active substance can be produced, allowing for dose reductionin 15% decrements. This technology guarantees the capability of the process, that is, capsules within required mass and content uniformity limits canbe produced/manufactured.
Cílem této studie bylo vyvinout off-line metodu pro stanovení tloušťky obalu. Na povrch tvrdých hypromelosových tobolek se nanesly polymerní obaly Eudragit® L 12.5 a Eudragit® S 12.5 v obalovacím zařízení se spodním nástřikem typu Wurster. Referenční hodnoty tloušťky obalu pro kalibrační vzorky se získaly mikroskopickou analýzou. Kalibrační model byl vytvořen pomocí chemometrických metod (PLS algoritmus). Na základě výsledků kalibrace a validace byly získány následující parametry: koeficienty determinace R2 byly větší než 0,98 a chyba křížové validace byla 6,6 µm (pro tloušťky obalu v rozsahu 15–235 µm) pro EL film a 8,3 µm (pro tloušťky obalu v rozsahu 30–230 µm) pro ES film. Získané výsledky potvrzují vhodnost blízké infračervené spektroskopie při kontrole kvality procesu obalování ve farmaceutickém průmyslu.
The aim of this study was to develop the method for off-line determination of hard capsules coating thickness. The polymer films studied were Eudragit® L 12.5 and Eudragit® S 12.5 applied on hypromellose capsules surface in a bottom-spray fluid-bed coater equipped with a Wurster column. The coating thickness reference values for calibration were obtained from microscopic analysis. Calibration model was created using partial least squares regression with six factors for Eudragit® L film and five factors for Eudragit® S film. The calibration and validation results led to following parameters: determination coefficients R2 were more than 0.98 and standard error of cross validation was 6.6 µm (coat thickness range was 15–235 µm) for Eudragit® L film and 8.3 µm (coat thickness range was 30–230 µm) for Eudragit® S film, respectively. Obtained results confirmed suitability of near infrared spectroscopy for coating process quality control in pharmaceutical industry.
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
- biologický transport MeSH
- časové faktory MeSH
- ileum metabolismus MeSH
- kofein farmakokinetika MeSH
- kolon metabolismus MeSH
- koncentrace vodíkových iontů MeSH
- kyseliny polymethakrylové chemie MeSH
- lékové transportní systémy metody MeSH
- léky s prodlouženým účinkem MeSH
- lidé MeSH
- methylcelulosa analogy a deriváty chemie MeSH
- rozpustnost MeSH
- tobolky chemie MeSH
- želatina chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Hard gelatin capsules belong to the most commonly used pharmaceutical solid dosage forms but their filling using capsule filling machines is known to present many problems to their operators. Such problems are caused by relatively complicated requirements on rheological properties of capsule fillings which vary with the filling technique used as those techniques rely on different physical principles. This review provides an overview of automated and semi-automated capsule-filling processes, emphasizing the aspects of processed particulate mixture behavior in the process; this description determines the process requirements on rheological properties of capsule fillings. Rheological properties which can be used to study and optimize the filling process are discussed, as well as methods of improving those properties using the flow additives.
Objectives: The abuse of benzodiazepines and Z-drugs reduces the quality of life of millions of addicted people worldwide. They cannot be discontinued abruptly due to harmful withdrawal symptoms. Detoxification is usually based on replacement of short/middle acting benzodiazepines or Z-drugs by diazepam and tapering the dose over time. In order to enhance patient adherence to an individual withdrawal plan, suitable diazepam dosage forms have to be available. Hard capsules containing an exact and uniform dose could be used for the relief of symptoms caused by altering the plasma level and overcoming psychogenic stress from the dose reduction. Methods: This work demonstrates that capsules with a content of diazepam ranging from 2.125mg to 0.492 mg (dose decreasing always by 15%) cannot be easily prepared by standard mortar technology in a pharmacy. To meet mass and content uniformity European Pharmacopoeia criteria, capsules were prepared by improved technology based on the preparation of binary blends of calcium phosphate anhydrous and diazepam in descending concentrations in a high-speed mixer (time 30 s) and densification of about 10% during filling of the capsules. Results: All batches (n=20) prepared by improved technology met the requirement for content uniformity compared with only nine batches prepared by standard mortar blender technology. Based on the process capability index, none of the samples prepared by standard technology fitted pharmacopeia limits at the statistically acceptable level. On the other hand, all batches prepared by improved technology exhibited acceptable process capability index. Conclusions: We have shown that at least 99.73% of batches prepared by our improved technology would meet the pharmacopoeia limits for content uniformity and are suitable for treatment of this type of addiction.
- Publikační typ
- časopisecké články MeSH
Coated hard capsules are becoming increasingly important for a number of reasons such as administration of new active ingredients, oral vaccination, colon drug delivery or their use in preclinical and clinical trials. The independency of coating composition on capsules filling is the major advantage of this dosage form. In our study, two types of hard capsules (gelatin and hypromellose) were coated by non-aqueous solutions of Eudragit L and S 12.5, respectively, to achieve intestinal and distal ileic drug delivery. Gelatin hard capsules were coated with Eudragit film either directly or using hydroxypropyl cellulose sub-coating prior to the final coating. Hypromellose capsules were coated directly. Coated capsules were evaluated for coating thickness by optical microscope and for dissolution in different pH media. Gelatin capsules do not seem to be suitable for direct coating with Eudragit due to insufficient film adhesion to the smooth capsule surface and a brittleness of formed films. These problems can be solved by hydroxypropyl celullose interlayer application. Hypromellose hard capsules could be directly easily coated with both Eudragit solutions. Dissolution of caffeine from coated capsules showed the potency for enteric delivery in gelatin capsules with interlayer and Eudragit L film in 7.5 and 10.0% concentrations and in hypromellose capsules coated with EudragitL in 5-17.5% coating levels. Gelatine capsules with interlayer and 10% Eudragit S film and hypromellose capsules only with high coating level (20%) provided potential distal ileum targeting of incorporated drug. Eudragit S film sprayed onto hypromellose capsules surface was brittle especially in the junction zone between capsule cap and body. Better plasticity of Eudragit S coating could be probably achieved using a different plasticizer.
Acta oto-laryngologica ; Supplement. 512
[1st ed.] 22 s. ; 28 cm
OBJECTIVE: This research aims to design and evaluate an enteric-coated hard capsule dosage form for targeted delivery of biological materials, such as FMT (fecal microbiota transplant) or live microbes, to the distal parts of the GIT. The capsules are designed to be internally protected against destruction by hydrophilic filling during passage through the digestive tract. METHODS: Hard gelatin capsules and DRcapsTMcapsules based on HPMC and gellan were used to encapsulate a hydrophilic body temperature-liquefying gelatin hydrogel with caffeine or insoluble iron oxide mixture. Different combinations of polymers were tested for the internal (ethylcellulose, Eudragit® E, and polyvinyl acetate) and external (Eudragit® S, Acryl-EZE®, and cellacefate) coating. The external protects against the acidic gastric environment, while the internal protects against the liquid hydrophilic filling during passage. Coated capsules were evaluated using standard disintegration and modified dissolution methods for delayed-release dosage forms. RESULTS: Combining suitable internal (ethylcellulose 1.0 %) and external (Eudragit® S 20.0 %) coating of DRcapsTM capsules with the wiping and immersion method achieved colonic release times. While most coated capsules met the pharmaceutical requirements for delayed release, one combination stood out. Colonic times were indicated by the dissolution of soluble caffeine (during 120-720 min) measured by the dissolution method, and capsule rupture was indicated by the release of insoluble iron oxide (after 480 min) measured by the disintegration method. This promising result demonstrates the composition's suitability and potential to protect the content until it's released, inspiring hope for the future of colon-targeted delivery systems and its potential for the pharmaceutical and biomedical fields. CONCLUSION: Innovative and easy capsule coatings offer significant potential for targeted drugs, especially FMT water suspension, to the GIT, preferably the colon. The administration method is robust and not considerably affected by the quantity of internal or external coatings. It can be performed in regular laboratories without specialized individual and personalized treatment equipment, making it a practical and feasible method for drug delivery.
- MeSH
- bakteriální polysacharidy chemie MeSH
- biokompatibilní materiály chemie MeSH
- celulosa * chemie analogy a deriváty MeSH
- deriváty hypromelózy chemie MeSH
- hydrofobní a hydrofilní interakce * MeSH
- hydrogely chemie MeSH
- kofein chemie aplikace a dávkování MeSH
- kolon * metabolismus MeSH
- kyseliny polymethakrylové chemie MeSH
- lékové transportní systémy * metody MeSH
- léky s prodlouženým účinkem chemie MeSH
- polymery chemie MeSH
- polyvinyly chemie MeSH
- tobolky * MeSH
- uvolňování léčiv * MeSH
- želatina * chemie MeSH
- železité sloučeniny chemie aplikace a dávkování MeSH
- Publikační typ
- časopisecké články MeSH
