Dry granulation
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In this study, the origins of granule content non-uniformity in the high-shear wet granulation of a model two-component pharmaceutical blend were investigated. Using acetaminophen as the active pharmaceutical ingredient (API) and microcrystalline cellulose as the excipient, the distribution of the API across the granule size classes was measured for a range of conditions that differed in the duration of the initial dry mixing stage, the overall composition of the blend and the wet massing time. The coarse granule fractions were found to be systematically sub-potent, while the fines were enriched in the API. The extent of content non-uniformity was found to be dependent on two factors - powder segregation during dry mixing and redistribution of the API between the granule size fractions during the wet massing phase. The latter was demonstrated in an experiment where the excipient was pre-granulated, the API was added later and wet massed. The content non-uniformity in this case was comparable to that obtained when both components were present in the granulator from the beginning. With increasing wet massing time, the extent of content non-uniformity decreased, indicating that longer wet massing times might be a solution for systems with a natural tendency for component segregation.
Full-thickness skin wounds are preferably allowed to heal under controlled hydration dressings such as hydrocolloids. It was hypothesized that a wet (liquid) environment rather than a dry or moist one would accelerate the wound healing process. We compared skin repair by secondary intention in full-thickness skin wounds in wet (saline), moist (hydrocolloid), and dry (gauze) conditions in an established porcine wound healing model. The study included three animals with a total of 70 wounds layered in a standardized fashion on the back of young Yorkshire pigs. Twelve days after wounding, 0 percent of dry, 20 percent of moist, and 86 percent of saline-treated wounds were completely reepithelialized (p values = 0.0046 and 0.027 for saline wounds compared with dry and moist wounds, respectively). The accelerated healing was caused at least in part by faster contraction in wet wounds (p value < 0.005 compared with that of other groups 9 and 12 days after wounding). Development of granulation tissue was faster in moist conditions than it was for dry and wet wounds. The thickness and number of cell layers of the newly formed epidermis were greater in dry and wet wounds than in moist ones. It was concluded that these full-thickness porcine skin wounds healed faster in a wet environment than in a moist one. Dry wounds healed more slowly than moist wounds. The basic mechanisms of skin wound repair were influenced by the treatment modality as demonstrated by the observed differences in granulation tissue formation, reepithelialization, and rate of wound contraction.
- MeSH
- epidermální buňky MeSH
- epidermis fyziologie MeSH
- epitel fyziologie MeSH
- granulační tkáň fyziologie MeSH
- hojení ran fyziologie MeSH
- kůže zranění MeSH
- prasata MeSH
- vlhkost * MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, P.H.S. MeSH
- srovnávací studie MeSH
Granulace je jedním z nejrozšířenějších technologických postupů při výrobě pevných perorálních lékových forem. S ohledem na bezpečnost práce při výrobě tablet s obsahem silně účinných léčiv se stále častěji využívá zařízení s uzavřenou konstrukcí, která během procesu výroby zabraňuje kontaminaci ovzduší a snižuje zdravotní riziko pro personál. Patří mezi ně jednostupňové vysokoobrátkové granulátory, fluidní granulátory a integrované granulační systémy spojující vysokoobrátkovou granulaci s fluidním sušením. Tato zařízení umožňují celý proces automatizovat a jsou vybavena automatickým čištěním. Jednotlivé technologie mají své výhody i nevýhody. Při zvážení instalace daných zařízení je třeba posoudit nejen procesní parametry, jako jsou robustnost, délka procesu, snadnost údržby, čistitelnost a technologické zázemí, ale i podrobně posoudit rozhodující kvalitativní požadavky na lék. U granulátů se jedná především o parametry, jako jsou hustota, tokové vlastnosti a distribuce velikosti částic a u tablet kromě běžných jakostních ukazatelů také o mechanickou odolnost a disoluci.
Granulation is one of the most widely spread technological procedures in the manufacture of solid oral dosage forms. With regard to the safety of work in the manufacture of tablets containing highly potent active ingredients, devices with a closed construction which during the process of manufacture prevent contamination of the surroundings and decrease health risk for the personnel are more widely used. They include one-step high-speed granulators, fluid granulators and integrated granulating systems connecting high-speed granulation with fluid drying. These devices make it possible to automate the whole process and they are equipped with automatic cleaning. The individual technologies possess certain advantages as well as disadvantages. When considering installation of these devices, it is necessary to evaluate not only the processual parameters such as robustness, length of process, easy maintenance, easy cleaning, and technological background, and also take into consideration the decisive qualitative requirements for the drug in detail. In granulates, they include primarily such parameters as density, flow properties and distribution of particle size, and in tablets, besides routine quality indices, also mechanical endurance and dissolution.
Tablety jsou nejpoužívanější lékovou formou. Jejich výhodou je dostupnost, snadné podání, dobrá stabilita a nízká cena. Nejjednodušší technologií pro výrobu tablet je přímé lisování, ačkoliv při použití této metody je nutné překonat určité obtíže, spojené zejména s hmotnostní a obsahovou stejnoměrností, disolucí a radiální pevností tablet. Společně zpracované pomocné látky obsahující běžně zpracované směsi plniv, pojiv, rozvolňovadel, lubrikantů a dalších pomocných látek, se v dnešní době používají stále častěji. Tyto směsi jsou vyráběny různými technologiemi, zejména sprejovým sušením, granulací ve fluidním loži, vlhkou granulací, granulací tavením, suchou granulací a společnou krystalizací. Tento článek popisuje pomocné látky, které se obvykle používají k vytvoření společně zpracovaných směsí, uvádí výrobní technologie a komerčně dostupné společně zpracované pomocné látky pro přímé lisování tablet.
Tablets are the most frequently employed dosage form. Their advantage lies in their availability, easy administration, good stability, and low price. The easiest technology to produce tablets is direct compression, even though the use of the method requires overcoming many obstacles, mainly related to content uniformity and variation of mass, disintegration, dissolution, and radial hardness of tablets. "Co-processed excipients", containing commonly processed blends of fillers, binders, disintegrants, lubricants, and other excipients are more and more widely used nowadays. These mixtures are manufactured by various technologies, chiefly by spray-drying, fluid bed granulation, wet granulation, melt granulation, dry granulation, and co-crystallisation. This review article lists excipients used usually to constitute co-processed excipients, technologies, and commercially available co-processed excipients for direct compression.
- Klíčová slova
- společně zpracované pomocné látky, lisování, fyzikální vlastnosti,
- MeSH
- farmaceutická technologie * metody MeSH
- farmaceutická vehikula MeSH
- farmaceutické pomocné látky * klasifikace MeSH
- tablety * MeSH
- Publikační typ
- přehledy MeSH
Polyhydroxyalkanoates (PHA) are storage polymers accumulated by numerous prokaryotes in form of intracellular granules. Native PHA granules are formed by amorphous polymer which reveals considerably higher elasticity and flexibility as compared to crystalline pure PHA polymers. The fact that bacteria store PHA in amorphous state has great biological consequences. It is not clear which mechanisms protect amorphous polymer in native granules from transition into thermodynamically favorable crystalline state. Here, we demonstrate that exposition of bacterial cells to particular stressors induces granules aggregation, which is the first but not sufficient condition for PHA crystallization. Crystallization of the polymer occurs only when the stressed bacterial cells are subsequently dried. The fact that both granules aggregation and cell drying must occur to induce crystallization of PHA indicates that both previously suggested hypotheses about mechanisms of stabilization of amorphous state of native PHA are valid and, in fact, both effects participate synergistically. It seems that the amorphous state of the polymer is stabilized kinetically by the low rate of crystallization in limited volume in small PHA granules and, moreover, water present in PHA granules seems to function as plasticizer protecting the polymer from crystallization, as confirmed experimentally for the first time by the present work.
As is the case with batch-based tableting processes, continuous tablet manufacturing can be conducted by direct compression or with a granulation step such as dry or wet granulation included in the production procedure. In this work, continuous manufacturing tests were performed with a commercial tablet formulation, while maintaining its original material composition. Challenges were encountered with the feeding performance of the API during initial tests which required designing different powder pre-blend compositions. After the pre-blend optimization phase, granules were prepared with a roller compactor. Tableting was conducted with the granules and an additional brief continuous direct compression run was completed with some ungranulated mixture. The tablets were assessed with off-line tests, applying the quality requirements demanded for the batch-manufactured product. Chemical maps were obtained by Raman mapping and elemental maps by scanning electron microscopy with energy-dispersive X-ray spectroscopy. Large variations in both tablet weights and breaking forces were observed in all tested samples, resulting in significant quality complications. It was suspected that the API tended to adhere to the process equipment, accounting for the low API content in the powder mixture and tablets. These results suggest that this API or the tablet composition was unsuitable for manufacturing in a continuous line; further testing could be continued with different materials and changes in the process.
BACKGROUND: Skin grafting may be necessary to close nonhealing skin wounds. This report describes a fast and minimally invasive method to produce minced skin suitable for transplantation to skin wounds. The technique was evaluated in an established porcine skin wound healing model and was compared to split-thickness skin grafts and suspensions of cultured and noncultured keratinocytes. MATERIALS AND METHODS: The study included 90 wounds on 3 pigs. Fluid-treated full-thickness skin wounds were grafted with minced skin, split-thickness skin grafts, noncultured keratinocytes, or cultured keratinocytes. Controls received either fluid or dry treatment. The wound healing process was analyzed in histologies collected at Days 8 to 43 postwounding. Wound contraction was quantified by photoplanimetry. RESULTS: Wounds transplanted with minced skin and keratinocyte suspension contained several colonies of keratinocytes in the newly formed granulation tissue. During the healing phase, the colonies progressed upward and reepithelialization was accelerated. Minced skin and split-thickness skin grafts reduced contraction as compared to keratinocyte suspensions and saline controls. Granulation tissue formation was also reduced in split-thickness skin-grafted wounds. CONCLUSIONS: Minced skin grafting accelerates reepithelialization of fluid-treated skin wounds. The technique is faster and less expensive than split-thickness skin grafting and keratinocyte suspension transplantation. Minced skin grafting may have implications for the treatment of chronic wounds.
- MeSH
- epitel zranění patologie MeSH
- hojení ran * MeSH
- keratinocyty cytologie transplantace MeSH
- kultivované buňky MeSH
- miniinvazivní chirurgické výkony přístrojové vybavení metody MeSH
- prasata MeSH
- transplantace kůže metody MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, P.H.S. MeSH
Xe-Derma je nové sterilní komerčně dostupné biologické krytí na rány odvozené z acelulární prasečí dermis. V hydratované formě vykazuje biomechanické vlastnosti podobné lidské dermis. Je distribuována v dehydratované formě a v tomto stavu může být uchovávána a skladována po dlouhou dobu. Jako dočasný biologický kožní kryt napomáhá hojení rány podporou migrace a proliferace keratinocytů a vytváří vhodné prostředí pro růst granulační tkáně v ráně. Xe-Derma může být užívána v léčbě povrchových i hlubokých popálenin, jako krytí na popáleniny po nekrektomii, odběrových míst kožních štěpů a povrchových mechanických zranění.
Xe-Derma is a new sterile commercially available biological wound dressing derived from acellular porcine dermis. In hydrated form it displays biomechanical features similar to human dermis. It is distributed in dry form and therefore it can be kept and stored for long periods of time. As a temporary biological skin cover it stimulates wound healing by supporting migration and proliferation of keratinocytes and creates an appropriate environment for the growth of granulation tissue in the wound. Xe-Derma can be used for treatment of superficial and deep dermal burns, as a cover of burn wounds after necrectomy, as a cover of donor sites and superficial mechanical wounds.
- MeSH
- biologické krytí * MeSH
- bolest MeSH
- čas MeSH
- dospělí MeSH
- hojení ran MeSH
- lidé středního věku MeSH
- lidé MeSH
- obvazy hydrokoloidní MeSH
- popálení * terapie MeSH
- povrch těla MeSH
- prasata MeSH
- senioři MeSH
- statistika jako téma MeSH
- stupeň závažnosti nemoci MeSH
- umělá kůže MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- kazuistiky MeSH
Laktitol patří mezi cukerné alkoholy, které se používají jako suchá pojiva ve výrobě tablet, a topředevším tablet žvýkacích. Přímo lisovatelná forma této látky je vodou granulovaný laktitol. Prácese zabývá studiem lisovatelnosti granulované formy laktitolu a vlivem různé koncentrace mazadlastearanu hořečnatého na pevnost a dobu rozpadu výlisků z této látky. Laktitol nelze lisovat bezpřídavku mazadla. Stearan hořečnatý, použitý ve dvou koncentracích, a to 0,4 % a 0,8 %, nezasáhlnegativně do pevnosti výlisků. Doba rozpadu tablet se prodlužovala s rostoucí koncentrací stearanu,ale nezávisle na lisovací síle.
Lactitol ranks among sugar alcohols which are employed as dry binders in the manufacture oftablets, particularly the chewable ones.Water-granulated lactitol is the directly compacting form ofthis substance. The present paper studies the compressibility of the granulated form of lactitol andthe effects of different concentrations of the lubricant magnesium stearate on the strength anddisintegration time of the compacts from his substance. Lactitol cannot be compressed without anadded lubricant. Magnesium stearate, employed in two concentrations, 0.4 % and 0.8 %, did notnegatively interfere with the strength of the compacts. The disintegration period of tablets wasprolonged with increasing stearate concentration, but independently of compression force.
Dekubity jsou léze kůže a měkkých tkání, které vznikají v místech vystavených nadměrnému tlaku. Dle klasifikace EPUAP/NPUAP je přítomnost nekrózy diagnostickým kritériem pro III. a IV. stadium dekubitů. Nekrotická tkáň v ráně blokuje hojení a tvorbu granulační tkáně, je zdrojem infekce, zápachu, představuje pro ránu závažnou biozátěž. Odstranění nekrózy (nekrektomie) a débridement spodiny dekubitu jsou důležitými kroky v přípravě spodiny rány (TIME koncepce). Zatímco výskyt vlhké nekrózy je v praxi často spojen s přítomností ranné infekce, suchá gangréna (eschara) hojení rány ovlivňuje v mnohem menším rozsahu a v některých případech může neinfikovaná eschara sloužit jako dočasný kryt dekubitu. Správné načasování débridementu spolu se zvolením vhodné metody débridementu výrazně ovlivňují výsledek léčby. I přes obecně známá pozitiva může débridement v určitých případech narušovat proces hojení: při overexcizi dochází k odstranění nekrózy vč. přiléhající vitální tkáně; při použití traumatizujících metod débridementu (nůžky, elektrokautel) dochází současně s odstraněním deficitní tkáně k narušení vitality spodiny vředu. V našem výzkumu jsme na tkáňovém modelu (experimentální část) i na skupině probandů (klinická část výzkumu) prokázali, že použití ostrého (skalpel) a hydrochirurgického débridementu (Versajet) urychluje débridement a zkracuje celkovou dobu potřebnou na reparaci tkání.
Pressure ulcers are skin and soft tissue lesions appearing in over-pressured places of the body. According to EPUAP/NPUAP classification, the presence of necrosis is a basic condition for determining the third and fourth stage of pressure ulcers. Necrotic tissue on the wound impedes the healing process and granulation tissue formation and is a source of infection and malodour. It poses a serious wound bioburden. Removal of the necrosis (necrectomy) and pressure ulcer bed debridement are important steps in a wound bed preparation (TIME concept). In practice, presence of moist necrosis (slough) is often being connected with presence of a wound infection, whereas dry gangrene (eschar) obstructs wound healing far less, and non-infected eschar can in some cases serve as a temporary pressure ulcer covering. Proper timing of debridement together with selectionof a correct debridement method noticeably affects treatment results. Despite of the well-known advantages, debridement can sometimes disrupt the healing process: over-excision leads to removal of the necrosis and even of the vital tissue close to the necrosis; debridement methods causing wound trauma (scissors, electrocautery) remove deficient tissues as well as they disrupt the wound bed vitality. Our research consisted of two parts: experimental (on a tissue model) and clinical part (on a group of probands). We have shown that sharp (scalpel) and hydrosurgical debridement (Vestajet) speed up the debridement process and shorten the total time for tissue recovery.
