Properties of bioadhesive ketoprofen liquid suppositories: preparation, determination of gelation temperature, viscosity studies and evaluation of mechanical properties using texture analyzer by 4 x 4 factorial design

WOS: 000328148400008PubMed ID: 24156540Context: Development and evaluation of thermosensitive and bioadhesive liquid suppositories containing ketoprofen (KP). Objective: This study was conducted to develope thermosensitive and bioadhesive liquid suppositories containing KP using poloxamer and different bioadhesive polymers and to investigate their gelation temperature, viscosity and mechanical properties. Materials and methods: Bioadhesive liquid suppositories were prepared by the cold method using poloxamer 407 (P 407), Poloxamer 188 (P 188) and various amounts of different bioadhesive polymers. Their gelation temperatures, viscosity values and mechanical properties were determined using texture analyzer by 4 x 4 factorial design. Results: It was seen that in presence of KP, gelation temperature of formulation P 407/P 188 (4/20%) significantly decreased from 64 to 37.1 degrees C. It is to be noted that addition of increasing concentrations of bioadhesive polymers lowered gelation temperature and its decrease was highest with addition of Carbopol 934 P (C). Results of texture profile analysis (TPA) showed that formulations containing C have significantly higher hardness and adhesiveness values than other bioadhesive formulations. According to TPA, gel structure of liquid suppository formulation F5, containing P 407/P 188/KP/C (4/20/2.5/0.8%), exhibited the greatest hardness, compressibilty, adhesiveness and besides greatest viscosity. Discussion and conclusion: According to mechanical properties and viscosity values, it was concluded that F5 could be a promising formulation.Research Foundation of Ege UniversityEge University [06/ECZ/005]The authors wish to thank Research Foundation of Ege University for financial support given to this study. Project number: 06/ECZ/005

In vitro-in vivo evaluation of in situ gelling and thermosensitive ketoprofen liquid suppositories

WOS: 000344741300007PubMed ID: 24096820The main objective of this study was to investigate the release and pharmacokinetic profiles of ketoprofen (KP) from developed thermosensitive and mucoadhesive liquid suppositories. Thermosensitive liquid suppositories were prepared using KP, poloxamer 407 (P 407), poloxamer 188 (P 188) and various amounts of different mucoadhesive polymers. In vitro release studies was monitored by the USP XXVI paddle method. The results thus obtained were evaluated kinetically and mechanism of release was analyzed. Identification of poloxamer gel localization in vivo was conducted using white male rabbits by adding 1 % methylene blue. For in vivo studies, twenty-four white male rabbits were randomly divided into three groups. The rabbits in each group were administered with liquid suppository F1 [P407/P188/KP (4/20/2.5 %)], F5 [P407/P188/KP/C (4/20/2.5/0.8 %)] or conventional suppository (F-C) into the rectum. The plasma concentration of KP was analyzed by high performance liquid chromatography (HPLC). C (max), AUC, MRT and T (max) were evaluated. The release of KP was variously affected by the mucoadhesive polymers. In vitro release studies showed that Carbopol 934 P(C) has significant effect on release rate among the mucoadhesive polymers. When the formulations were evaluated kinetically, different kinetic models were obtained. Formulation F6 [P407/P188/KP/C (4/20/2.5/1.6 %)] which contains the highest C concentration and very high viscosity, shows a significantly better fit with Higuchi kinetic model. n value of this formulation was also found approximately 0.5. n exponent results of the other formulations showed that KP might be released from the suppositories by non-Fickian diffusion. Identification of poloxamer gel localization in vivo showed that the suppositories remain in the rectum without leakage after administration. With regard to the results of in vivo studies, the AUC(6 -> 14) values of KP in liquid suppository containing C are significantly higher than those in liquid suppository without C. MRT0 -> 24 and MRT0 -> a values of liquid suppository containing C are significantly higher than those in liquid suppository without C and conventional suppository. Conventional suppository and liquid suppository without C significantly gave faster time to reach the maximum plasma concentrations of KP. With regard to the in vitro and in vivo experiments, liquid suppository formulation F5 might be a promising formulation for the development of an effective rectal dosage form.Research Foundation of Ege UniversityEge University [06/ECZ/005]The authors wish to thank Research Foundation of Ege University for financial support given to this study. Project number: 06/ECZ/005

Development and Characterization of Naproxen-Loaded Poly(vinyl alcohol) Nanofibers Crosslinked with Polycarboxylic Acids

WOS: 000419058800004Poly(vinyl alcohol) (PVA) hydrogel nanofibers are a potential candidate for textile-based drug-release applications. Polycarboxylic acids 1,2,3,4-butanetetracarboxylic acid (BTCA) and citric acid (CA) are low-cost alternatives reported to easily crosslink electrospun PVA hydrogel. These can be directly added into the spinning solutions. One of the most efficient non-steroidal anti-inflammatory drugs (NSAIDs), Naproxen (NAP), was selected as a model drug for this study. The release mechanisms of drug-loaded electrospun PVA nanofibers are based on the diffusion of the drugs through the swollen PVA fibrous matrix and the release due to partial dissolution of the matrix. Control over drug-release characteristics can be provided through partial crosslinking of the PVA fibrous matrix

Acceleration of in vitro dissolution studies of sustained release dosage form of theophylline and in vitro-in vivo evaluations in terms of correlations

WOS: 000300772200008PubMed ID: 21739190The aim of the study was to accelerate the dissolution of the sustained release dosage forms using both elevated temperature and high rpm rates. Teokap (R) SR 200 mg pellets were tested by in vitro sustained and accelerated dissolution studies using USP XXIII rotating paddle method. Sustained dissolution studies were carried out for 12 h in phosphate buffer at 37 +/- 0.5 degrees C and 50 rpm. Accelerated dissolution studies were performed for 48 min in distilled water at 90 +/- 1 degrees C and 250 rpm. The results obtained from accelerated and sustained dissolution studies were correlated using both linear and linear kinetic correlation methods by a computer program. While r(2) and maximum error between calculated and observed drug release rates were found to be 0.9129 and 15.9%, respectively, in linear correlation method, these values were observed as 0.9938 and 3.6%, respectively, in linear kinetic correlation method. In vivo plasma concentration data were obtained from six New Zealand rabbits after administration of a single dose of Teokap (R) SR 200 mg pellet. Then, the results of in vivo study were evaluated with in vitro accelerated and sustained dissolution results by applying them to in vitro-in vivo linear correlations. As a result of these correlations, it was shown that the in vitro correlation plots were very similar to the plot which was obtained by the in vivo study (f(2) = 73.81-77.11). This study suggested a way to prevent the loss of time for routine dissolution studies of sustained release preparations for quality control procedures using in vitro accelerated dissolution tests. The storage and quarantine periods of the product in process and process controls in the manufactories could be shortened by this method. Calculation of the in vivo performance of sustained release dosage forms using the results of the accelerated dissolution studies may be counted as another advantage of the method