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The purpose of this research was to study whether the bioavailability of ursodeoxycholic acid could be improved by administering ursodeoxycholic acid–phospholipid complex (UDCA–PLC) orally to rats. A central composite design approach was used for process optimization in order to obtain the acceptable UDCA–PLC. The physicochemical properties of the complex obtained by optimal parameters were investigated by means of scanning electron microscopy; X-ray diffraction. The pharmacokinetic parameters; bioavailability studies were conducted in rats of UDCA after oral administration of UDCA–PLC; UDCA tablet. Multiple linear regression analysis for process optimization revealed that the acceptable UDCA–PLC was obtained wherein the optimal values of X 1, X 2; X 3 were 3, 60°C; 3 h, respectively. The XRD studies of UDCA–PLC obtained by the optimal parameters demonstrated that UDCA; phospholipids in the UDCA–PLC were combined by non-covalent bonds, not form new compounds. But pharmacokinetic parameters of the complex in rats were T max 1.6 h, C max 0.1346 μg/ml, 11.437 μg·h/ml, respectively. The relative bioavailability of UDCA of UDCA–PLC was increased by 241%,compared with the reference ursodeoxycholic acid tablet.
Peng-Fei Yue1 Wen-Jin Zhang1 Hai-Long Yuan1 Email:yhlpharm@126.com Ming Yang2 Wei-Feng Zhu2 Pei-Lie Cai3 Xiao-He Xiao1
[1] 302 Hospital of PLA&PLA Institute of Chinese Materia Medica, Beijing, 100039, China ;[2] Key Lab of Modern Preparation of TCM, Ministry of Education, Nanchang, 330004, China ;[3] Huiren Group, Shanghai, 201203, China
2008.9.1 done
Inclusion complexes between dexamethasone acetate (DMA), a poorly water soluble drug,; β-cyclodextrin (βCD) were obtained to improve the solubility; dissolution rate of this drug. Phase-solubility profile indicated that the solubility of DMA was significantly increased in the presence of βCD (33-fold); was classified as AL-type, indicating the 1:1 stoichiometric inclusion complexes. Solid complexes prepared by different methods (kneading, coevaporation, freeze drying); physical mixture were characterized by differential scanning calorimetry, thermogravimetry, infrared absorption; optical microscopy. Preparation methods influenced the physicochemical properties of the products. The dissolution profiles of solid complexes were determined; compared with those DMA alone; their physical mixture, in three different mediums: simulated gastric fluid (pH 1.2), simulated intestinal fluid (pH 7.4); distilled water. The dissolution studies showed that in all mediums DMA presented an incomplete dissolution even in four hours. In contrast, the complexes formed presented a higher dissolution rate in simulated gastric fluid (SGF pH 1.2), which indicate that these have different ionization characteristics. According to the results, the freeze–dried; kneaded products exhibited higher dissolution rates than the drug alone, in all the mediums.
Mayara M. Doile1 Keila A. Fortunato1 Iára C. Schmücker1 Sacha K. Schucko1 Marcos A.S. Silva2 Patrik O. Rodrigues1Email:patrikoening@gmail.com
[1] Departamento de Farmácia, Universidade da Regio de Joinville, Bom Retiro, CEP 88040-900 Joinville, Santa Catarina, Brazil ;[2] Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina, Florianópolis, Brazil
The purpose of this research was to design oral controlled release (CR) matrix tablets of zidovudine (AZT) using hydroxypropyl methylcellulose (HPMC), ethyl cellulose (EC); carbopol-971P (CP); to study the effect of various formulation factors on in vitro drug release. Release studies were carried out using USP type 1 apparatus in 900 ml of dissolution media. Release kinetics were analyzed using zero-order, Higuchi’s square root; Ritger–Peppas’ empirical equations. Release rate decreased with increase in polymer proportion; compression force. The release rate was lesser in formulations prepared using CP (20%) as compared to HPMC (20%) as compared to EC (20%). No significant difference was observed in the effect of pH of dissolution media on drug release from formulations prepared using HPMC or EC, but significant difference was observed in CP based formulations. Decrease in agitation speed from 100 to 50 rpm decreased release rate from HPMC; CP formulations but no significant difference was observed in EC formulations. Mechanism of release was found to be dependent predominantly on diffusion of drug through the matrix than polymer relaxation incase of HPMC; EC formulations, while polymer relaxation had a dominating influence on drug release than diffusion incase of CP formulations. Designed CR tablets with pH independent drug release characteristics; an initial release of 17–25% in first hour; extending the release up to 16–20 h, can overcome the disadvantages associated with conventional tablets of AZT.
Punna Rao Ravi1 Email:rpunnarao@bits-pilani.ac.in Udaya Kanth Kotreka1 Email:kotrekau@duq.edu Ranendra Narayan Saha1 Email:rnsaha@bits-pilani.ac.in
[1] Pharmacy Group, Birla Institute of Technology; Science, Pilani, Rajasthan, India
The objective of this study was to develop a multiunit sustained release dosage form of diltiazem using a natural polymer from a completely aqueous environment. Diltiazem was complexed with resin; the resinate-loaded carboxymethyl xanthan (RCMX) beads were prepared by interacting sodium carboxymethyl xanthan (SCMX), a derivatized xanthan gum, with Al[+3] ions. The beads were evaluated for drug entrapment efficiency (DEE); release characteristics in enzyme free simulated gastric fluid (SGF, HCl solution, pH 1.2); simulated intestinal fluid (SIF, USP phosphate buffer solution, pH 6.8). Increase in gelation time from 5 to 20 min; AlCl3 concentration from 1 to 3% decreased the DEE respectively from 95 to 79%; 88.5 to 84.6%. However, increase in gum concentration from 1.5 to 2.5% increased the DEE from 86.5 to 90.7%. The variation in DEE was related to displacement of drug from the resinate by the gel forming Al[+3] ions. While 75–82% drug was released in 2 h in SGF from various beads, 75 to 98% drug was released in 5 hour in SIF indicating the dependence of drug release on pH of dissolution media. Although the beads maintained their initial integrity throughout the dissolution process in both media, as evident from scanning electron microscopic studies, the faster release in SGF was accounted for higher swelling of the beads in SGF than in SIF. When release data (up to 60%) was fitted in power law expression, the drug release was found to be controlled by diffusion with simultaneous relaxation phenomena.
Somasree Ray1 Sabyasachi Maiti2 Biswanath Sa2Email:biswanathsa2003@yahoo.com
[1] Gupta College of Technological Sciences, Ashram More, Asansol-1, India ;[2] Centre for Advanced Research in Pharmaceutical Sciences, Department Of Pharmaceutical Technology, Jadavpur University, Kolkata, 700032, India ;[3] Division of Pharmaceutics, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700032, India
The purpose of this research was to develop the hydrodynamically balanced delivery system of Clarithromycin (CLA) which, after oral administration should have the ability to prolong gastric residence time with the desired in vitro release profile for the localized action in the stomach, in the treatment of Helicobacter pylori (H.pylori) mediated peptic ulcer. By applying wet granulation technique floating tablets of Clarithromycin were prepared. The proportion of sodium bicarbonate was varied to get the least possible lag time, also the polymer part varied to get the desired release. In vivo radiographic studies were performed with Barium sulphate loaded formulation to justify the increased gastric residence time of the dosage form in the stomach, based on the floating principle. The formulation developed using 66.2% Clarithromycin, 12% HPMC K4M polymer, 8% sodium bicarbonate gave floating lag time less than 3 min with a floating time of 12 h,; an in vitro release profile very near to the desired release. X-ray studies showed the enhanced gastric residence time of the tablet to 220±30 min. The mechanism of release of Clarithromycin from the floating tablets is anomalous diffusion transport; follows zero order kinetics. In vivo radiographic studies suggest that the tablet has increased gastric residence time for the effective localized action of the antibiotic (Clarithromycin) in the treatment of H.pylori mediated peptic ulcer.
Muralidhar Nama1 Ch ra Sekhar Rao Gonugunta1 Prabhakar Reddy Veerareddy1Email:vpreddyindia@yahoo.com
[1] Pharmaceutics, St. Peter’s Institute of Pharmaceutical Sciences, Warangal, Andhra Pradesh, India ;[2] St. Peter’s Institute of Pharmaceutical Sciences, Vidya Nagar, Hanmakonda, A.P., 506001, India
In this study an attempt was made to prepare mucoadhesive microcapsules of gliclazide using various mucoadhesive polymers designed for oral controlled release. Gliclazide microcapsules were prepared using sodium alginate; mucoadhesive polymer such as sodium carboxymethyl cellulose (sodium CMC), carbopol 934P or hydroxy propylmethyl cellulose (HPMC) by orifice-ionic gelation method. The microcapsules were evaluated for surface morphology; particle shape by scanning electron microscope. Microcapsules were also evaluated for their microencapsulation efficiency, in vitro wash-off mucoadhesion test, in vitro drug release; in vivo study. The microcapsules were discrete, spherical; free flowing. The microencapsulation efficiency was in the range of 65–80%; microcapsules exhibited good mucoadhesive property in the in vitro wash off test. The percentage of microcapsules adhering to tissue at pH 7.4 after 6 h varied from 12–32%, whereas the percentage of microcapsules adhering to tissue at pH 1.2 after 6 h varied from 35–68%. The drug release was also found to be slow; extended for more than 16 h. In vivo testing of the mucoadhesive microcapsules in diabetic albino rats demonstrated significant antidiabetic effect of gliclazide. The hypoglycemic effect obtained by mucoadhesive microcapsules was for more than 16 h whereas gliclazide produced an antidiabetic effect for only 10 h suggesting that mucoadhesive microcapsules are a valuable system for the long term delivery of gliclazide.
S. K. Prajapati1 Purnima Tripathi1 Udhumansha Ubaidulla2 Vikas An 3 Email:vikas.pharmaceutics@gmail.com
[1] Department of Pharmaceutics, Institute of Pharmacy, Bundelkhand University, Jhansi, Uttar Pradesh, India ;[2] Research; Development, Reddy’s Laboratory, Hyderabad, Andhra Pradesh, India ;[3] Department of Pharmaceutics, Seth G.L. Bihani S.D. College of Technical Education, Sri Ganganagar, Rajasthan, India
There is a critical need for development of novel delivery systems to facilitate the translation of nucleic acid-based macromolecules into clinically-viable therapies. The aim of this investigation was to develop; evaluate a novel nanoparticles-in-microsphere oral system (NiMOS) for gene delivery; transfection in specific regions of the gastrointestinal (GI) tract. Plasmid DNA, encoding for the enhanced green fluorescent protein (EGFP-N1), was encapsulated in type B gelatin nanoparticles. NiMOS were prepared by further protecting the DNA-loaded nanoparticles in a poly(epsilon-caprolactone) (PCL) matrix to form microspheres of less than 5.0 μm in diameter. In order to evaluate the biodistribution following oral administration, radiolabeled ([111]In-labeled) gelatin nanoparticles; NiMOS were administered orally to fasted Balb/C mice. The results of biodistribution studies showed that, while gelatin nanoparticles traversed through the GI tract fairly quickly with more than 54% of the administered dose per gram localizing in the large intestine at the end of 2 h, NiMOS resided in the stomach; small intestine for relatively longer duration. Following oral administration of EGFP-N1 plasmid DNA at 100 μg dose in the control; test formulations, the quantitative; qualitative results presented in this study provide the necessary evidence for transfection potential of NiMOS upon oral administration. After 5 days post-administration, transgene expression in the small; large intestine of mice was observed. Based on these results, NiMOS show significant potential as novel gene delivery vehicle for therapeutic; vaccination purposes.
Mayank D. Bhavsar1 Mansoor M. Amiji1 Email:m.amiji@neu.edu
[1] Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, 110 Mugar Life Sciences Building, Boston, MA 02115, USA
The purpose of this research was to study the feasibility of the new image analysis method in the particle size determination of the granules. The method is capable of forming a three-dimensional topographic image of a sample surface from a digital picture. In the method, a flat granule bed surface was illuminated from three different directions, using the three primary colors (red, green,; blue). One color picture was taken by a digital camera, after which a topographic image of the object surface was constructed. The particle size distribution was then calculated from the image data. The particle size analysis method was tested both off-line; on-line. Off-line particle size measurement results determined by the image analysis method corresponded quite well to those of sieve analysis in the size fraction range 250–1,000 μm. In on-line application, images were successfully retrieved; median granule size trend could be calculated; followed during fluid bed granulations.
Tero N?rv?nen1 Email:tero.narvanen@orionpharma.com Kari Sepp?l?1 Osmo Antikainen2 Jouko Yliruusi2
[1] Orion Corporation, Orion Pharma, Orionintie 1, P.O. Box 65, 02101 Espoo, Finland ;[2] Division of Pharmaceutical Technology, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, 00014 Helsinki, Finland
There is a critical need for development of novel delivery systems to facilitate the translation of nucleic acid-based macromolecules into clinically-viable therapies. The aim of this investigation was to develop; evaluate a novel nanoparticles-in-microsphere oral system (NiMOS) for gene delivery; transfection in specific regions of the gastrointestinal (GI) tract. Plasmid DNA, encoding for the enhanced green fluorescent protein (EGFP-N1), was encapsulated in type B gelatin nanoparticles. NiMOS were prepared by further protecting the DNA-loaded nanoparticles in a poly(epsilon-caprolactone) (PCL) matrix to form microspheres of less than 5.0 μm in diameter. In order to evaluate the biodistribution following oral administration, radiolabeled ([111]In-labeled) gelatin nanoparticles; NiMOS were administered orally to fasted Balb/C mice. The results of biodistribution studies showed that, while gelatin nanoparticles traversed through the GI tract fairly quickly with more than 54% of the administered dose per gram localizing in the large intestine at the end of 2 h, NiMOS resided in the stomach; small intestine for relatively longer duration. Following oral administration of EGFP-N1 plasmid DNA at 100 μg dose in the control; test formulations, the quantitative; qualitative results presented in this study provide the necessary evidence for transfection potential of NiMOS upon oral administration. After 5 days post-administration, transgene expression in the small; large intestine of mice was observed. Based on these results, NiMOS show significant potential as novel gene delivery vehicle for therapeutic; vaccination purposes.
Mayank D. Bhavsar1 Mansoor M. Amiji1 Email:m.amiji@neu.edu
[1] Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, 110 Mugar Life Sciences Building, Boston, MA 02115, USA
The purpose of this research was to study the feasibility of the new image analysis method in the particle size determination of the granules. The method is capable of forming a three-dimensional topographic image of a sample surface from a digital picture. In the method, a flat granule bed surface was illuminated from three different directions, using the three primary colors (red, green,; blue). One color picture was taken by a digital camera, after which a topographic image of the object surface was constructed. The particle size distribution was then calculated from the image data. The particle size analysis method was tested both off-line; on-line. Off-line particle size measurement results determined by the image analysis method corresponded quite well to those of sieve analysis in the size fraction range 250–1,000 μm. In on-line application, images were successfully retrieved; median granule size trend could be calculated; followed during fluid bed granulations.
Tero N?rv?nen1 Email:tero.narvanen@orionpharma.com Kari Sepp?l?1 Osmo Antikainen2 Jouko Yliruusi2
[1] Orion Corporation, Orion Pharma, Orionintie 1, P.O. Box 65, 02101 Espoo, Finland ;[2] Division of Pharmaceutical Technology, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, 00014 Helsinki, Finland