A drug dissolution profile is one of the most important characteristics of the dosage form with controlled drug release. Obtained dissolution data can be used for evaluation of a drug release rate and mechanism of its release from the dosage form. Nowadays various mathematical models can be used for this purpose. An accordance with a particular mathematical model is determined by regression characteristics and by the relevance of the regression model parameter estimation. Since the dissolution curves are not linear with the exception of the zero-order kinetics, the transformation of dependencies into a linear form is often performed. However, linearization is connected with a change in the deviation magnitudes and the resulting function does not minimize squared deviations. The main aim of this manuscript was to show an overview of basic mathematical models in a form suitable for nonlinear regression which work with original experimental data and to summarize basic steps for determining the drug release mechanism and rate constants.

Due to the additional particle coalescence in the coating, changes in the dissolution profile occur over time in the formulations coated by aqueous ethylcellulose latex. Dry thermal treatment (DT) of the coating can be used as a prevention of this process. Alternatively, it is advisable to take advantage of the synergistic effect of high humidity during wet treatment (WT), which substantially accelerates the film formation. This can be a problem for time-controlled systems, which are based on the coating rupture due to the penetration of water into the core causing the increase in the system volume. This process can begin already during the WT, which may affect the coating adversely. The submitted work was focused on the stability testing of two pellet core compositions: pellets containing swelling superdisintegrant sodium carboxymethyl starch (CMS) and pellets containing osmotically active polyethylene glycol (PEG). Another objective was to identify the treatment/storage condition effects on the pellet dissolution profiles. These pellets are intended to prevent hypoglycemia for patients with diabetes mellitus and therefore, besides the excipients, pellet cores contain 75% or 80% of glucose. The pellet coating is formed by ethylcellulose-based latex, which provides the required lag time (120-360 min). The sample stability was evaluated depending on the pellet core composition (PEG, CMS) for two types of final pellet coating treatment (DT or WT). Scanning electron microscopy and Raman microspectroscopy revealed the penetration of glucose and polyethylene glycol from the core to the PEG pellet surface after WT. For the CMS sample, significant pellet swelling after WT (under the conditions of elevated humidity) was statistically confirmed by the means of stereomicroscopic data evaluation. Therefore, the acceleration of dissolution rate during the stress tests is caused by the soluble substance penetration through the coating in the case of PEG pellets or by dosage form volume increase in the case of CMS pellets. The observed mechanisms can be generally anticipated during the stability testing of the ethylcellulose coated dosage forms. The aforementioned processes do not occur after DT and the pellets are stable in the environment without increased humidity.

• MeSH
• celulosa analogy a deriváty   chemie   MeSH
• chemie farmaceutická MeSH
• glukosa chemie   farmakologie   MeSH
• hypoglykemie prevence a kontrola   MeSH
• léky implantované chemie   MeSH
• léky s prodlouženým účinkem MeSH
• polyethylenglykoly chemie   MeSH
• pomocné látky chemie   MeSH
• povrchové vlastnosti MeSH
• příprava léků metody   MeSH
• rozpustnost MeSH
• škrob analogy a deriváty   chemie   MeSH
• stabilita léku MeSH
• uvolňování léčiv MeSH
• velikost částic MeSH
• vysoká teplota MeSH
• Publikační typ
• časopisecké články MeSH

The purpose of this experimental work was the development of hydrophilic-lipophilic matrix tablets for controlled release of slightly soluble drug represented here by diclofenac sodium (DS). Drug dissolution profile optimization provided by soluble filler was studied. Matrix tablets were based on cetyl alcohol as the lipophilic carrier, povidone as the gel-forming agent, and common soluble filler, that is lactose or sucrose of different particle size. Physical properties of tablets prepared by melt granulation and drug release in a phosphate buffer of pH 6.8 were evaluated. In vitro studies showed that used filler type, filler to povidone ratio and sucrose particle size influenced the drug release rate. DS dissolution profile could be changed within a wide range from about 50% per 24 hours to almost 100% in 10 hours. The release constant values confirmed that DS was released from matrices by the diffusion and anomalous transport. The influence of sucrose particle size on the drug release rate was observed. As the particle size decreased, the drug release increased significantly and its dissolution profile became more uniform. Soluble fillers participated in the pore-forming process according to their solubility and particle size. Formulations containing 100 mg of the drug, 80 mg of cetyl alcohol, 40 mg of povidone, and 80 mg of either lactose or sucrose (particle size 250-125 microm) were considered optimal for 24-hour lasting dissolution of DS.

• MeSH
• antiflogistika nesteroidní aplikace a dávkování   chemie   MeSH
• časové faktory MeSH
• diklofenak aplikace a dávkování   chemie   MeSH
• laktosa chemie   MeSH
• léky s prodlouženým účinkem MeSH
• mastné alkoholy chemie   MeSH
• nosiče léků chemie   MeSH
• pomocné látky chemie   MeSH
• povidon chemie   MeSH
• rozpustnost MeSH
• sacharosa chemie   MeSH
• tablety MeSH
• velikost částic MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Uvolňování léčiva nejen z tuhých perorálních lékových forem se zkouší in vitro disolučním testem. Podmínky provádění disoluce a limity, které musí jednotlivé lékové formy splnit jsou přesně stanoveny. Srovnatelné uvolňování léčiva z originálního léku a generika předchází zkoušce bioekvivalence, na základě které může být generický lék považován za podobný s originálním produktem. Ve studii se porovnávaly vybrané perorální originální léky používané v kardiologii se svými generiky disoluční zkouškou. Hodnotily se léky bez a s modifikovaným uvolňováním léčiva. Z první skupiny léků se porovnával lék Zorem® se svými generiky obsahující amlodipin, lékem Orcal® a Hipres® a originální lék Sectral® s lékem Acecor® obsahující acebutolol. Zatímco lék Hipres® uvolňoval v porovnání se svým originálním lékem Zorem® statisticky významně větší množství léčiva a tablety léku Orcal® nevyhověly podmínkám první úrovně hodnocení disoluční zkoušky, generický lék Acecor® byl srovnatelný se svým originálním lékem Sectral® a jeho disoluční profil byl navíc méně ovlivňován změnou pH disolučního média. Ze skupiny léků s řízeným uvolňováním léčiva se porovnávaly léky Betaloc® ZOK a Emzok® obsahující metoprolol. Hodnotily se disoluční profily ve 3 médiích s rostoucí hodnotou pH napodobující pasáž léku gastrointestinálním traktem. Ve všech 3 disolučních médiích se uvolňovalo léčivo z léku Betaloc® ZOK kinetikou nultého řádu minimálně 12 hodin na rozdíl od léku Emzok®. Zjistilo se, že jejich disoluční profily nejsou podobné v žádném disolučním médiu.

The drug release from the dosage forms is determined using in vitro dissolution test. The conditions and limitations of dissolution tests for each dosage form are strictly given. The equivalent drug release from original and generic product proved using dissolution tests is followed by a bioequivalence study. It proves the similarity between the original product and its generic. In this experimental work selected cardio-active original brands and their generics were compared using dissolution test. Two different types of oral dosage forms were evaluated: tablets without and with modified drug release. In the first group original brand Zorem® was compared with two generics Orcal® and Hipres® containing amlodipine and also original brand Sectral® with its generic Acecor® containing acebutolol. While Hipres® released significantly higher amount of drug when compared with Zorem®, Orcal® have not fulfiled the conditions of the first line class dosage form. Generical Acecor® succeeded in comparison with its original brand Sectral® and its dissolution profile was even less influenced by changes in pH values of the dissolution media. The second group was represented controlled drug release products with metoprolol. Three dissolution media with increasing pH values, imitating the passage of the drug in GIT were used. The drug released from Betaloc® ZOK followed zero order kinetic in all three media at least twelve hours contrary to its generic Emzok®. Dissolution profiles of Betaloc® ZOK and Emzok® were not similar.

• Klíčová slova
• Zoren, Orcal, Hipres, Sectral, Acecor, Betalor, ZOK, Emzok,
• MeSH
• acebutolol aplikace a dávkování   farmakokinetika   MeSH
• amlodipin aplikace a dávkování   farmakokinetika   MeSH
• generika aplikace a dávkování   farmakokinetika   MeSH
• hodnocení léčiv MeSH
• kardiologie MeSH
• lékové formy MeSH
• metoprolol aplikace a dávkování   farmakokinetika   MeSH
• Publikační typ
• přehledy MeSH
• srovnávací studie MeSH

Particles preparation from biodegradable polymers as carriers for the controlled release of drugs has been the focus of many investigations and the subject of a growing field of research in recent years. The aim of this study was to develop and optimize the preparation of oxycellulose beads containing diclofenac sodium as a model drug. Particle size, surface, drug content and encapsulation efficiency were evaluated, drug dissolution profiles were measured and drug release mechanism estimated. The prepared oxycellulose beads were uniform in size with encapsulation efficiency ranging from 53.2 to 74.9%. The lower temperature of the crosslinking solution and its saturation with diclofenac sodium increased the encapsulation efficiency, especially when both parameters were combined. The application of ultrasound had a negative effect on drug encapsulation. The dissolution of diclofenac sodium in pH 1.2 was close to zero as its solubility in this medium is very limited. The drug release in pH 6.8 lasted from 10 to 16 h showing biphasic behavior with a significant lag time. T1/2 decreased with increasing encapsulation efficiency and ultrasound application. Diclofenac sodium was released from the prepared oxycellulose particles by diffusion as well as by erosion process; ahigh correlation was found with zero order kinetics.

• MeSH
• antiflogistika nesteroidní chemie   MeSH
• chemie farmaceutická MeSH
• chlorid vápenatý chemie   MeSH
• difuze MeSH
• diklofenak chemie   MeSH
• farmaceutická technologie metody   MeSH
• kinetika MeSH
• koncentrace vodíkových iontů MeSH
• léky s prodlouženým účinkem MeSH
• methylcelulosa analogy a deriváty   chemie   MeSH
• nosiče léků * MeSH
• povrchové vlastnosti MeSH
• reagencia zkříženě vázaná chemie   MeSH
• rozpustnost MeSH
• teplota MeSH
• ultrazvuk MeSH
• velikost částic MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Warfarín je stále rozsiahle diskutovaným liečivom s úzkym terapeutickým indexom. Jeho generické náhrady boli v minulosti príčinou krvácavosti. Ako príčina boli diskutované kvalita substancie a miera obsahovej rovnorodosti. Kvalitu substancie je možné posúdiť vhodnou disolučnou metódou. Doteraz existuje pre tablety s obsahom warfarínu oficiálna miešadlová disolučná metóda s vodným médiom, ktorá nemá rozlišujúci charakter. V priebehu prvých 15 minút u nej dochádza k takmer úplnému uvoľneniu účinnej látky z liekovej formy, čím je znemožnené vzájomné porovnanie tabliet od rôznych výrobcov alebo sledovanie prípadných zmien v priebehu stabilitných testov. Z literatúry je známa aj metóda s médiom s pH 6,8, ktorá sa odporúča ako vhodná alternatíva. Cieľom tejto práce bolo vyskúšať, či táto metóda pri dvoch rýchlostiach otáčok (50 a 25 rpm) bude vhodná k výpočtom faktorov podobnosti a rozdielnosti a prípadne bude mať rozlišujúci charakter vzhľadom k veľkosti častíc účinnej látky a pevnosti tabliet. Za týmto účelom boli vyrobené tablety s obsahom 10 mg sodnej soli warfarínu vo forme kryštalického klathrátu s izopropanolom. Pripravené tablety sa líšili veľkosťou častíc účinnej látky (d50 = 4,8, resp. 22,5 μm) a ich radiálnou pevnosťou (30, resp. 100 N). Obsahová rovnorodosť tabliet, bola overená pomocou indexu spôsobilosti procesu (Cpk) a Bergumovej metódy. Bolo potvrdené, že disolučné médium s pH 6,8 umožňuje vzájomné porovnanie disolučných profilov pomocou výpočtov faktorov podobnosti a rozdielnosti, no za daných podmienok nemá rozlišujúci charakter.

Warfarin is intensively discussed drug with narrow therapeutic index. In the past, its generic substitution was identified as a cause of bleeding. Altered quality of the active substance or varying drug content was discussed. The substance quality can be evaluated with adequate dissolution method. An official dissolution method with aqueous medium exists, however this method is non-discriminatory. In the first 15 minutes the whole amount of the active pharmaceutical ingredient is released from a tested dosage form, which does not allow comparison between tablets from different producers and it also makes difficult to track the changes throughout stability testing. In the literature, there is a well known method using pH 6.8 buffer, which seems to be a suitable alternative to water. The aim of this study was to prove, that this alternative medium, when two stirring speeds for dissolution (50 or 25 rpm) are used, will be suitable for calculation of similarity and difference factor and if it will be eventually discriminatory with regard to particle size and radial hardness. For this purpose we prepared tablets with 10 mg of warfarin sodium in form of crystalline clathrate with isopropanol. Tablets differed by particle size of active pharmaceutical ingredient (d50 = 4.8, or d50 = 22.5 μm respectively) and by radial hardness (30, or 100 N respectively). The content uniformity of the tablets was determined using process capability index (Cpk) and Bergum method. It was confirmed that the dissolution medium with pH of 6.8 allows comparison of dissolution profiles by similarity and difference factors but under given conditions it is not discriminatory.

• Klíčová slova
• disoluční metoda, disoluční metoda, faktor rozdílnosti, faktor podobnosti, radiální pevnost,
• MeSH
• koncentrace vodíkových iontů MeSH
• kontrola léčiv a omamných látek metody   MeSH
• rozpouštědla chemie   MeSH
• tablety analýza   farmakokinetika   MeSH
• terapeutická ekvivalence * MeSH
• terapeutický index léčiva MeSH
• uvolňování léčiv * MeSH
• velikost částic MeSH
• výzkum MeSH
• warfarin * chemie   MeSH

• Publikační typ
• abstrakt z konference MeSH

• MeSH
• Aspirin MeSH
• chemické modely MeSH
• rozpustnost MeSH
• vyprazdňování žaludku MeSH

The purpose of this study was to specify critical parameters (physicochemical characteristics) of drug substance that can affect dissolution profile/dissolution rate of the final drug product manufactured by validated procedure from various batches of the same drug substance received from different suppliers. The target was to design a sufficiently robust drug substance specification allowing to obtain a satisfactory drug product. For this reason, five batches of the drug substance and five samples of the final peroral drug products were analysed with the use of solid state analysis methods on the bulk level. Besides polymorphism, particle size distribution, surface area, zeta potential, and water content were identified as important parameters, and the zeta potential and the particle size distribution of the drug substance seem to be critical quality attributes affecting the dissolution rate of the drug substance released from the final peroral drug formulation.

• MeSH
• chemické jevy * MeSH
• mikroskopie elektronová rastrovací MeSH
• rozpustnost MeSH
• uvolňování léčiv * MeSH
• velikost částic MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

CONTEXT: The preparation of liquisolid systems (LSS) represents a promising method for enhancing a dissolution rate and bioavailability of poorly soluble drugs. The release of the drug from LSS tablets is affected by many factors, including the disintegration time. OBJECTIVE: The evaluation of differences among LSS containing varying amounts and types of commercially used superdisintegrants (Kollidon® CL-F, Vivasol® and Explotab®). MATERIALS AND METHODS: LSS were prepared by spraying rosuvastatin solution onto Neusilin® US2 and further processing into tablets. Varying amounts of superdisintegrants were used and the differences among LSS were evaluated. The multiple scatter plot method was used to visualize the relationships within the obtained data. RESULTS AND DISCUSSION: All disintegrants do not showed negative effect on the flow properties of powder blends. The type and concentration of superdisintegrant had an impact on the disintegration time and dissolution profiles of tablets. Tablets with Explotab® showed the longest disintegration time and the smallest amount of released drug. Fastest disintegration and dissolution rate were observed in tablets containing Kollidon® CL-F (≥2.5% w/w). Also tablets with Vivasol® (2.5-4.0% w/w) showed fast disintegration and complete drug release. CONCLUSION: Kollidon® CL-F and Vivasol® in concentration ≥2.5% are suitable superdisintegrants for LSS with enhanced release of drug.

• MeSH
• anticholesteremika aplikace a dávkování   chemie   MeSH
• farmaceutické pomocné látky chemie   MeSH
• povidon chemie   MeSH
• příprava léků MeSH
• rosuvastatin kalcium aplikace a dávkování   chemie   MeSH
• rozpustnost MeSH
• silikáty chemie   MeSH
• škrob analogy a deriváty   chemie   MeSH
• sloučeniny hliníku chemie   MeSH
• sloučeniny hořčíku chemie   MeSH
• tablety chemie   MeSH
• uvolňování léčiv MeSH
• Publikační typ
• časopisecké články MeSH