Physicochemical characterization and dissolution study of solid dispersions of Lovastatin with polyethylene glycol 4000 and polyvinylpyrrolidone K30.
Department of Pharmaceutics, S. K. Patel College of Pharmaceutical Education and Research, Ganpat University, Ganpat Vidyanagar, Kherva, Gujarat, India. email@example.com
Solid dispersions in water-soluble carriers have attracted considerable interest as a means of improving the dissolution rate, and hence possibly bioavailability, of a range of hydrophobic drugs. The aim of the present study was to improve the solubility and dissolution rate of a poorly water-soluble drug, Lovastatin, by a solid dispersion technique. Solid dispersions were prepared by using polyethylene glycol 4000 (PEG 4000) and polyvinylpyrrolidone K30 (PVP K30) in different drug-to-carrier ratios. Dispersions with PEG 4000 were prepared by fusion-cooling and solvent evaporation, whereas dispersions containing PVP K30 were prepared by solvent evaporation technique. These new formulations were characterized in the liquid state by phase solubility studies and in the solid state by differential scanning calorimetry, X-ray powder diffraction, and FT-IR spectroscopy. The aqueous solubility of Lovastatin was favored by the presence of both polymers. The negative values of the Gibbs free energy and enthalpy of transfer explained the spontaneous transfer from pure water to the aqueous polymer environment. Solid-state characterization indicated Lovastatin was present as amorphous material and entrapped in polymer matrix. In contrast to the very slow dissolution rate of pure Lovastatin, the dispersion of the drug in the polymers considerably enhanced the dissolution rate. This can be attributed to improved wettability and dispersibility, as well as decrease of the crystalline and increase of the amorphous fraction of the drug. Solid dispersion prepared with PVP showed the highest improvement in wettability and dissolution rate of Lovastatin. Even physical mixture of Lovastatin prepared with both polymers also showed better dissolution profile than that of pure Lovastatin. Tablets containing solid dispersion prepared with PEG and PVP showed significant improvement in the release profile Lovastatin compared with tablets containing Lovastatin without PEG or PVP.
Biodegradable ocular inserts for sustained delivery of brimonidine tartarate: preparation and in vitro/in vivo evaluation.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Egypt.
The bioavailability of therapeutic agents from eye drops is usually limited due to corneal barrier functions and effective eye protective mechanisms. Therefore, the current study aims to enhance ocular bioavailability of brimonidine, a potent antiglaucoma drug, through the preparation of ocular inserts. Solvent casting technique was employed to prepare the inserts using polyvinylpyrrolidone K-90 (PVP K-90) as film-forming polymer blended with different viscosity grades of bioadhesive polymers namely hydroxypropyl methycellulose, carbopol, sodium alginate, and chitosan. The prepared ocular inserts were evaluated for various physicochemical parameters, swelling behavior, and in vitro release patterns. Sodium alginate-based ocular inserts revealed the most sustainment in drug release (99% at 6 h), so it was selected for further modifications via coating it, on one side or dual sides, using hydrophobic film composed of either ethylcellulose or Eudragit RSPO. The obtained in vitro release results for the modified ocular inserts revealed that ethylcellulose is superior to Eudragit RSPO in terms of brimonidine release sustainment effect. Ocular inserts composed of 7% PVP K-90, 1.5% low molecular weight sodium alginate with or without ethylcellulose coat were able to sustain the in vitro release of brimonidine. Their therapeutic efficacy regarding intraocular pressure (IOP) lowering effect when inserted in albino rabbits eyes showed superior sustainment effect compared with that of brimonidine solution. Furthermore, due to both the mucoadhesive property and the drug sustainment effect, the one-side-coated ocular insert showed more IOP lowering effect compared with that of its non-coated or dual-side-coated counterpart.
Dissolution and solid-state characterization of poorly water-soluble drugs in the presence of a hydrophilic carrier.
College of Pharmacy, Southwestern Oklahoma State University, Weatherford, 73096, USA. firstname.lastname@example.org
The aim of this study was to investigate the effects of a hydrophilic carrier on the solid-state and dissolution characteristics of poorly water-soluble drugs. Three poorly water-soluble drugs, ibuprofen, carbamazepine, and nifedipine, were studied in combination with hydroxypropyl cellulose (HPC), a low molecular weight hydrophilic polymer, without the use of solvent. A 1:1 drug-polymer ratio was used to evaluate the percent drug release, crystallinity, and wettability. A drug-polymer ratio of 1:4 was also used in co-grinding process to evaluate the effect of polymer levels on drug release. Dissolution studies were carried out in deionized water. Mean dissolution time (MDT) was calculated, and statistical analysis of MDTs was done following a single factor one-way analysis of variance. The dissolution rate of the drugs was enhanced by several folds by the simple process of co-grinding with HPC. X-ray diffraction studies were done to investigate the effects of physical and co-ground mix with HPC on the crystallinity of the drugs, which indicated a partial loss in crystallinity upon grinding. Differential scanning calorimetry studies were performed in order to identify possible solid-state interactions between the respective drugs and HPC. Wettability of the drugs by a 0.5% aqueous HPC solution was compared with that of water and n-hexane using the "Washburn method." Increased wetting and hydrophilization of the drugs by HPC, enlarged surface area due to particle size reduction, and a decrease in the degree of crystallinity were identified as the likely contributors to dissolution rate enhancement.
J Drug Target. 2011 Feb 8;: 21303222
Graduate Institute of Clinical Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
The aim of this work was to investigate whether the oral bioavailability and brain regional distribution of (+)-catechin could be improved by utilizing elastic liposomes. Liposomes containing soy phosphatidylcholine, cholesterol, and Tween 80 in the presence of 15% ethanol were prepared by a thin-film method and subsequent sonication and extrusion. The size, zeta potential, and stability of the liposomes in simulated gastrointestinal (GI) media were characterized. The mean size of liposomes was 35?70?nm, which decreased with an increase in the Tween 80 concentration. The zeta potential of the system was about?15 mV. More than 80% of the (+)-catechin was entrapped in the aqueous core of liposomes produced with 1% Tween 80. Liposomes entrapping (+)-catechin remained stable in the presence of GI fluids, especially in simulated intestinal fluid. The liposomes showed suppressed and sustained release of (+)-catechin compared with that from an aqueous solution. The aqueous control and liposomes were orally administered to rats. The blood level of liposomal (+)-catechin was enhanced at a later stage after administration compared with the free control. In the experiment on the brain distribution, liposomes with elastic properties showed 2.9- and 2.7-fold higher (+)-catechin accumulations compared with the aqueous solution in the cerebral cortex and hippocampus, respectively. Greater compound accumulations with liposomes were also detected in the striatum and thalamus. The experimental results suggest that elastic liposomes may offer a promising strategy for improving (+)-catechin delivery via oral ingestion.
Physicochemical characterization of gliclazide-macrogol solid dispersion and tablets based on optimized dispersion.
Department of Pharmaceutics, Faculty of Pharmacy, Kuwait University, Safat, Kuwait.
Background: This study investigated the physical interaction of gliclazide (GLC) with a hydrophilic carrier, that is, macrogol [polyethylene glycol (PEG)]. Different molecular weights of PEG (4000, 10,000, and 20,000) were used in different drug : carrier weight ratios (1 : 1, 1 : 2, 1 : 5, and 1 : 10). Method: Preliminary screening was done by phase solubility studies to characterize the liquid state interaction between the drug and the carrier. Solid dispersions (SDs) of GLC and PEG in different ratios were prepared by fusion technique and by physical mixing. The solid-state interaction between the drug and the carrier was examined by performing differential scanning calorimetry and Fourier transform infrared spectroscopic studies. SD with satisfactory characteristics was selected for the formulation of tablets by wet granulation method and compared with the commercial brand for in vitro dissolution. Results: It was evident from phase solubility studies that the drug solubility increased linearly with increasing PEG concentrations. In vitro dissolution of GLC improved significantly in the SDs prepared by fusion method as compared with the original drug and physical mixtures. Scanning electron microscopy images showed well-defined changes in the surface topography of GLC, thus confirming the effective formation of a fused binary system. The SD tablets showed a significant improvement in the drug release profile than that of the commercial brand. Conclusion: It was thus concluded that SD formulations of GLC can be successfully used to design a solid dosage form of the drug, which would have significant advantages over the current marketed tablets.
Evaluation and modeling of the eutectic composition of various drug-polyethylene glycol solid dispersions.
Department of Industrial and Physical Pharmacy, School of Pharmacy, Purdue University, West Lafayette, Indiana, USA.
The purpose of this study was to gain a better understanding of which factors contribute to the eutectic composition of drug-polyethylene glycol (PEG) blends and to compare experimental values with predictions from the semi-empirical model developed by Lacoulonche et al. Eutectic compositions of various drug-PEG 3350 solid dispersions were predicted, assuming athermal mixing, and compared to experimentally determined eutectic points. The presence or absence of specific interactions between the drug and PEG 3350 were investigated using Fourier transform infrared (FT-IR) spectroscopy. The eutectic composition for haloperidol-PEG and loratadine-PEG solid dispersions was accurately predicted using the model, while predictions for aceclofenac-PEG and chlorpropamide-PEG were very different from those experimentally observed. Deviations in the model prediction from ideal behavior for the systems evaluated were confirmed to be due to the presence of specific interactions between the drug and polymer, as demonstrated by IR spectroscopy. Detailed analysis showed that the eutectic composition prediction from the model is interdependent on the crystal lattice energy of the drug compound (evaluated from the melting temperature and the heat of fusion) as well as the nature of the drug-polymer interactions. In conclusion, for compounds with melting points less than 200 degrees C, the model is ideally suited for predicting the eutectic composition of systems where there is an absence of drug-polymer interactions.
Innovation of novel sustained release compression-coated tablets for lornoxicam: formulation and in vitro investigations.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
OBJECTIVE The objective of this study was to modify the release characteristics of lornoxicam, a highly potent nonsteroidal anti-inflammatory drug, by preparing compression-coated tablets (CCTs) that provide complete drug release that starts in the stomach to rapidly alleviate the painful symptoms and continues in the intestine to maintain prolonged analgesic effect as well as meets the reported sustained release specifications. METHODS Each of the prepared CCTs was composed of a sustained release tablet core and an immediate release coat layer. Amorphous, well-characterized, freeze-dried solid dispersion of lornoxicam with polyvinylpyrrolidone K-30 was employed in the coat layer to attain an initial rapid dissolution of lornoxicam in the stomach, assuring rapid onset of analgesic effect. Compritol ATO 888, a lipophilic matrix-forming material, was included in the core tablets to sustain lornoxicam release. Lactose was also incorporated into these core tablets to ensure complete release of lornoxicam in a time period comparable to the gastrointestinal residence time. RESULTS All the prepared CCTs showed acceptable physical properties that complied with compendial requirements. On the basis of in vitro drug release studies, performed in simulated gastric and intestinal fluids in sequence to mimic the gastrointestinal transit, CCTs belonging to formulations F3 CCTs and F4 CCTs were able to show the desired release profile. CONCLUSION This study demonstrated the possibility of modulating lornoxicam release using CCTs to meet the reported sustained release specifications.
Pharm Dev Technol. 2009 Jul 10;: 19589124
Preparation, characterization and dissolution studies of fast release diclofenac sodium tablets from PVP solid dispersions.
Maria C Lamas, Darío Leonardi, Osvaldo A Lambri, Georgina Bassani, María G Barrera, Raúl E Bolmaro, Claudio J Salomon
Departamento Farmacia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario.
Diclofenac sodium is a non-steroidal anti-inflammatory drug widely used in the treatment of ankylosing spondylitis, rheumatoid arthritis and osteoarthritis. In this context, a rapid onset of action is required. Thus, the aim of this study was to formulate diclofenac sodium-PVP K-30 fast release tablets from solid dispersions. The physical state and drug:carrier interactions were analyzed by X-ray diffraction and scanning electron microscopy and stability upon storage was also studied. Dissolution rate of diclofenac sodium from solid dispersions was markedly enhanced by increasing the polymer concentration.
Intraorally fast-dissolving particles of a poorly soluble drug: Preparation and in vitro characterization.
Riikka Laitinen, Eero Suihko, Kaisa Toukola, Mikko Björkqvist, Joakim Riikonen, Vesa Pekka Lehto, Kristiina Järvinen, Jarkko Ketolainen
Department of Pharmaceutics, University of Kuopio, Kuopio, Finland.
In this study, the dissolution rate of a poorly soluble drug, perphenazine (PPZ) was improved by a solid dispersion technique to permit its usage in intraoral formulations. Dissolution of PPZ (4mg) in a small liquid volume (3ml, pH 6.8) within one minute was set as the objective. PVP K30 and PEG 8000 were selected for carriers according to the solubility parameter approach and their 5/1, 1/5 and 1/20 mixtures with PPZ (PPZ/polymer w/w) were prepared by freeze-drying from 0.1. N HCl solutions. The dissolution rate of PPZ was improved with all drug/polymer mixture ratios compared to crystalline or micronized PPZ. A major dissolution rate improvement was seen with 1/5 PPZ/PEG formulation, i.e. PPZ was dissolved completely within one minute. SAXS, DSC and XRPD measurements indicated that solid solutions of amorphous PPZ in amorphous PVP or in partly amorphous PEG were formed. DSC and FTIR studies suggested that PPZ dihydrochloride salt was formed and hydrogen bonding was occurred between PPZ and the polymers. It was concluded that molecular mixing together with salt formation promoted the dissolution of PPZ, especially in the case of the 1/5 PPZ/PEG dispersion, making it a promising candidate for use in intraoral formulations.
Redispersible, dry emulsion of lovastatin protects against intestinal metabolism and improves bioavailability.
Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
AIM To prepare a redispersible, dry emulsion (DE) and investigate whether it can improve intestinal stability and oral absorptive efficiency of the poorly water-soluble lovastatin (Lov). METHODS Phosal 53 MCT, Tween 80, and starch sodium octenyl succinate were employed as the oil phase, emulsifying agent, and matrix material, respectively. The redispersible, DE of Lov (Lov-DE) was prepared by spray drying the submicron emulsion of Lov. The characteristics of DE and the in vitro drug release were studied. The protective effects on the metabolism of Lov- DE and reference formulations, including the Lov suspension and the hydroxypropyl-beta-cyclodextrin (CD) complex were investigated in microsomes and the gut wall of male Sprague-Dawley (SD) rats. The bioavailability in SD rats was evaluated simultaneously. RESULTS Lov-DE in distilled water was reconstituted compared with the submicron emulsion of Lov before spray drying, and remained almost unchanged after 3 months' storage at room temperature. Compared with the Lov suspension, the in vitro Lov dissolution of both the redispersible, DE and CD complex increased obviously. Compared with control formulations, the metabolism studies carried out in vitro and in vivo confirmed that the redispersible, DE presented remarkable protective effects as indicated by the decreased metabolism rate of Lov. Lov-DE showed a 1.83-fold and 1.44-fold higher the area under the curve(AUC0-8 h)of Lov compared with that of the Lov suspension and CD complex in SD rats, respectively. CONCLUSION Lov-DE reduced the metabolism of Lov in the small intestine and improved its oral absorption in SD rats.
Other papers by authors:
Draft Genome Sequence of Pontibacter sp. nov. BAB1700, a Halotolerant, Industrially Important Bacterium.
Gujarat State Biotechnology Mission, Department of Science & Technology, Udyog Bhavan, Gandhinagar, Gujarat, India.
Pontibacter sp. nov. BAB1700 is a halotolerant, Gram-negative, rod-shaped, pink-pigmented, menaquinone-7-producing bacterium isolated from sediments of a drilling well. The draft genome sequence of the strain, consisting of one chromosome of 4.5 Mb, revealed vital gene clusters involved in vitamin biosynthesis and resistance against various metals and antibiotics.
Preparation, characterization and in vitro dissolution study of Nitrazepam: Cyclodextrin inclusion complex.
Department of Pharmaceutics and Pharmaceutics Technology, S. K. Patel College of Pharmaceutical Education and Research, Ganpat University, Kherva, Gujarat, India.
The objectives of this research were to prepare and characterize inclusion complexes of Nitrazepam with Hydroxypropyl-β-cyclodextrin (HPβCD) and Sulfobutyl ether β-cyclodextrin (SBEβCD) to study the effect of complexation on the dissolution rate of Nitrazepam, a water-insoluble drug. The phase solubility profile of Nitrazepam with Hydroxypropyl- β-cyclodextrin and Sulfobutyl ether β-cyclodextrin was an AP-type, indicating the formation of 2:1 stoichiometric inclusion complexes. Gibbs free energy values were all negative, indicating the spontaneous nature Nitrazepam solubilization and their value decreased with increase in the cyclodextrin concentration, demonstrating that the reaction conditions became more favorable as the concentration of cyclodextrins increased. Complexes of Nitrazepam were prepared with cyclodextrin using various methods such as physical mixing, kneading, spray-drying and lyophilization. The complexes were characterized by Differential scanning calorimetry, Fourier-transform infrared, scanning electron microscopy and powder X-ray diffraction studies. These studies indicated that a complex prepared by lyophilization had successful inclusion of the Nitrazepam molecule into the cyclodextrin cavity. Complexation resulted in a marked improvement in the solubility and wettability of Nitrazepam. Among all the samples, a complex prepared with Sulfobutyl ether β-cyclodextrin by lyophilization had the greatest improvement in the in vitro rate of Nitrazepam dissolution. The mean dissolution time for Nitrazepam decreased significantly after preparing complexes. The similarity factor indicated a significant difference between the release profiles of Nitrazepam from complexes, physical mixtures and plain Nitrazepam. To conclude that, the tablets containing complexes prepared with Cyclodextrins had significant improvement in the release profile of Nitrazepam as compared to tablets containing Nitrazepam without cyclodextrin.
Solubility enhancement of benfotiamine, a lipid derivative of thiamine by solid dispersion technique.
S.K. Patel College of Pharmaceutical Education and Research, Ganpat Vidyanagar, Mehsana-Gozariya Highway, Kherva, Gujarat, India.
The present study was aimed to increase the solubility of the poorly water soluble drug benfotiamine using hydrophilic polymers (PVP K-30 and HPMC E4). Solid dispersions were prepared by kneading method. Phase solubility study, in-vitro dissolution of pure drug, physical mixtures and solid dispersions were carried out. PVP and HPMC were found to be effective in increasing the dissolution of Benfotiamine in solid dispersions when compared to pure drug. FT-IR, differential scanning calorimetry and X-ray diffractometry studies were carried out in order to characterize the drug and solid dispersion. To conclude that, the prepared solid dispersion of PVP-30 may to effectively used for the enhancement of solubility of poorly water soluble drugs such as benfotiamine.
ISRN Pharm. 2012 ;2012 :528079 22852100
Rajesh A Keraliya, Chirag Patel, Pranav Patel, Vipul Keraliya, Tejal G Soni, Rajnikant C Patel, M M Patel
Department of Pharmaceutics, Kalol Institute of Pharmacy, Gujarat, Kalol 382721, India.
Conventional drug delivery systems are known to provide an immediate release of drug, in which one can not control the release of the drug and can not maintain effective concentration at the target site for longer time. Controlled drug delivery systems offer spatial control over the drug release. Osmotic pumps are most promising systems for controlled drug delivery. These systems are used for both oral administration and implantation. Osmotic pumps consist of an inner core containing drug and osmogens, coated with a semipermeable membrane. As the core absorbs water, it expands in volume, which pushes the drug solution out through the delivery ports. Osmotic pumps release drug at a rate that is independent of the pH and hydrodynamics of the dissolution medium. The historical development of osmotic systems includes development of the Rose-Nelson pump, the Higuchi-Leeper pumps, the Alzet and Osmet systems, the elementary osmotic pump, and the push-pull system. Recent advances include development of the controlled porosity osmotic pump, and systems based on asymmetric membranes. This paper highlights the principle of osmosis, materials used for fabrication of pumps, types of pumps, advantages, disadvantages, and marketed products of this system.
Clin Radiol. 2012 May 17;: 22607956
Department of Radiology, The Royal United Hospital Bath, Combe Park, Bath BA1 3NG, United Kingdom.
Drug Dev Ind Pharm. 2011 Apr 6;: 21466414
Department of Pharmaceutics and Pharmaceutical Technology, S.K. Patel College of Pharmaceutical Education and Research, Ganpat University, Kherva, Gujarat, India and *Department of Pharmaceutics, Kalol Institute of Pharmacy, Kalol, Gujarat, India.
The goal of diabetes therapy today is to achieve and maintain as near normal glycemia as possible to prevent the long-term microvascular and macrovascular complications of an elevated blood glucose. A newly developed inlay osmotic pump tablet (IOPT) can deliver glipizide (GLZ) and metformin HCl (MET) gradually in controlled manner. The aim of present investigation was to prepare the IOPT that can deliver >75% of GLZ in 2 h, whereas MET released after 2 h and sustained up to 12 h. In the present work, HP-β-CD was used to modify the solubility of GLZ before incorporating in the osmotic system and MET was spray-dried with HPMC A15C to modify its release profile, flow property, and compressibility. Various parameters mainly G(75%)(75% GLZ release), t(LMET)(lag time of MET release from device), Q(10 h)(percent of MET released within 10 h), and RSQ(ZERO)(R(2) of release data fitted to zero-order equation) were used to compare different formulations. The effects of different formulation variables, that is, osmagents, concentration of hydrophilic polymer, diameter of drug releasing orifice, and coating composition on the drug release profile were investigated. The release rate of GLZ could be effectively modified by the addition of sodium carbonate and sodium chloride, whereas the release rate of MET was adjusted by dual-coating system and by addition of hydrophilic polymer. The developed inlay osmotic system could be effective in the multidrug therapy of diabetes by delivering both drugs in a controlled manner.
Subhash S Vaghani, Mitesh Gurjar, Sachin Singh, Sunil Sureja, Shailesh Koradia, N P Jivani, M M Patel
Smt. R. B. Patel Mahila, Atkot, Gujarat, India. email@example.com
The purpose of the present study was to explore the combined effect of chemical enhancers and iontophoresis on the in vitro permeation of acyclovir gel across porcine skin. Acyclovir gel was formulated using carbopol 940 and hydroxypropyl methylcellulose K4M (HPMC K4M). Effect of drug concentration on the delivery of acyclovir was examined. Increasing drug concentration of acyclovir enhanced its flux across the skin. Incorporation of permeation enhancers (menthol, n-methyl-2-pyrrolidone and polyethylene glycol 400) into the gel resulted in enhanced acyclovir permeation when combined with iontophoresis. Menthol showed the highest drug permeation and when combined with iontophoresis it significantly increased the acyclovir skin permeation.
Mechanisms of potentiation of Angiotensin II-induced contractile response of isolated rat aorta by hydrogen peroxide and tert-butyryl hydroperoxide.
Department of Pharmacology, Shree S. K. Patel College of Pharmaceutical Education and Research, Ganpat Vidyanagar, Kherva-382711, Gujarat, India.
OBJECTIVE To study the mechanism involved in hydrogen peroxide (H(2)O(2)) or tert-butyl hydroperoxide (t-BHP)-induced potentiation of the Ang II-mediated contraction of isolated rat thoracic aorta. MATERIALS AND METHODS Thoracic aorta was isolated from the Sprauge dawley rats (300-320 gm), cut spirally and response to Ang II (5 x 10(-8)M) was taken in the absence and presence of H(2)O(2)(10(-6)M) and t-BHP (10(-5)M). To explore the probable mechanism of H(2)O(2) and t-BHP-induced potentiation of Ang II-mediated contractile response, different blockers such as losartan (AT(1) receptor blocker; 1 muM), catalase (H(2)O(2) scavenger; 500 U/ml), lercanidipine (L-type calcium channel blocker; 1 muM), geinistein (tyrosine kinase inhibitor; 100 muM), and indomethacin (cyclo-oxygenase inhibitor; 10 muM) were used. RESULTS In spiral preparation of rat thoracic aorta, H(2)O(2)(10(-6)M) and t-BHP (10(-5)M) did not produce the contraction as such. However, when they are added simultaneously with Ang II (5 x 10(-8) M), they potentiated the contractile response of the Ang II. Catalase (500 U/ml) partially antagonized the Ang-II-induced contraction, as well as antagonized the potentiation induced by H(2)O(2). Losartan (1 muM) and lercanidipine (1 muM) antagonized the Ang II-induced contractile response without affecting H(2)O(2)(10(-6)M)-mediated potentiation. Geinistein (100 muM) antagonized H(2)O(2)(10(-6)M)-mediated potentiation, but it slightly decreased the Ang II response. Losartan (1 muM) and lercanidipine (1 muM) and Geinistein (100 muM) antagonized the Ang II-induced contractile response but not t-BHP-mediated potentiation. Indomethacin antagonized t-BHP-mediated potentiation without affecting much of Ang II response. CONCLUSION From the above-mentioned results, we can reasonably conclude that H(2)O(2) and t-BHP potentiated the contraction induced by the Ang II. H(2)O(2)-induced potentiation of Ang II response may be mediated through tyrosine kinase activation and t-BHP through the activation of cyclo-oxygenase enzyme.
Considerations for introduction of a rotavirus vaccine in Oman: rotavirus disease and economic burden.
S A Al Awaidy, S Bawikar, S Al Busaidy, S Baqiani, I Al Abedani, R Varghese, H S Abdoan, H Al Abdoon, S Bhatnagar, K S Al Hasini, P Mohan, S Shah, E Elamir, J Klena, S F Ahmed, N Teleb, U Parashar, M M Patel
Departments of Communicable Disease Surveillance and Control, Cairo, Egypt.
Rotavirus is the most common cause of fatal childhood diarrhea worldwide. We provide the first estimates of the health care and economic burden of severe rotavirus disease in Oman. We conducted active, hospital-based surveillance of rotavirus disease at 11 regional public hospitals in Oman, using the guidelines suggested by the generic World Health Organization protocol. From July 2006 through June 2008, all children aged <5 years who were hospitalized for acute gastroenteritis were enrolled in the surveillance program, and their stool samples were tested for rotavirus using a commercially available enzyme immunoassay (ID EIA Rotavirus Test; Dako Diagnostics). Rotavirus was detected in samples from 1712 (49%) of 3470 children. These children were hospitalized for a median of 3 days for severe diarrhea. A marked seasonal peak was evident with a majority of the cases occurring from December through May. Of the rotavirus cases, 69% occurred in children aged 6-17 months. We identified a diverse strain pattern in Oman, with G2 (37%), G1 (38%), and G9 (11%) accounting for most of typeable strains. By our burden estimates, the Omani government spends an estimated US$791,817 and US$1.8 million annually to treat rotavirus-associated diarrhea in the outpatient and hospital settings, respectively. A rotavirus vaccination program might substantially reduce the burden of severe diarrhea among children in Oman.
Center for Free Radical Biology, University of Birmingham at Alabama, Birmingham, AL, USA.
The oxidation of lipids is an autocatalytic process consisting of a number of well-defined interrelated chemical reactions. Its importance has long been recognized in the food and polymer industry, and recent advances in the understanding of vascular diseases have shown that lipid peroxidation also contributes to human disease. The various chemical stages of the reaction offer several therapeutic targets for inhibition, and from the structural characteristics of phytoestrogens it is anticipated that they should exhibit antioxidant properties. Alone, it is not sufficient for compounds such as the phytoestrogens to exhibit biological activity as antioxidants; the criteria that should be satisfied for this mechanism to be relevant biologically are discussed.
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Solid-state characterization of lacidipine/PVP K(29/32) solid dispersion primed by solvent co-evaporation.
Department of Formulation Development, Regulated Market, Cadila Pharmaceuticals Limited, Dholka, Ahmedabad, India.
BACKGROUND Lacidipine (LCDP) is a 1,4-dihydropyridine derivative categorized as an anti-hypertensive Ca2+ channel blocker having very low solubility, and thus very low oral bioavailability, which presents a challenge to the formulation scientists. Homogeneous distribution of poorly water-soluble drugs like LCDP in polyvinylpyrrolidone (PVP), a hydrophilic carrier, is definitely a suitable way to improve the bioavailability of such drugs. MATERIALS AND METHODS The aim of the study was to develop a combined thermal, imaging, and spectroscopic approach, and characterize physical state, dissolution behavior, and elucidation of drug-PVP interaction in LCDP/PVP solid dispersion (SD) using differential scanning calorimetry (DSC), X-ray diffractometry (XRD), fourier transform infrared (FTIR) spectroscopy, and hot stage microscopy (HSM), which is the prerequisite for the development of a useful drug product. RESULTS Dissolution studies of LCDP and its physical mixture with PVP showed less than 50% release even after 60 min, whereas SD of LCDP/PVP ratio of 1:10% w/w showed complete dissolution within 45 min. DSC and powder XRD proved the absence of crystallinity in LCDP/PVP SD at a ratio of 1:10% w/w. The FTIR spectroscopy indicated formation of hydrogen bond between LCDP and PVP. In the SD FTIR spectra, the -NH stretching vibrations and the -C=O stretch in esteric groups of LCDP shift to free -NH and C=O regions, indicating the rupture of intermolecular hydrogen bond in the crystalline structure of LCDP. CONCLUSION Solid-state characterization by HSM, DSC, XRD, and FTIR studies, in comparison with corresponding physical mixtures, revealed the changes in solid state during the formation of dispersion and justified the formation of high-energy amorphous phase.
Department of Pharmacy, Faculty of Technology, Osmania University, Hyderabad, India.
BACKGROUND Efavirenz is the preferred nonnucleotide reverse transcriptase inhibitor for first-line antiretroviral treatment in many countries. It is orally active and is specific for human immunodeficiency virus type 1. Its effectiveness can be attributed to its long half-life, which is 52-76 h after multiple doses. The drug is having poor water solubility. The formulation of poorly soluble drug for oral delivery will be one of the biggest challenges for formulation scientists in the research field. Among the available approaches, the solid dispersion technique has often proved to be the most commonly used method in improving dissolution and bioavailability of the drugs because of its simplicity and economy in preparation and evaluation. MATERIALS AND METHODS Solid dispersions were prepared by solvent evaporation and physical mixture methods by using polyethylene glycol as the hydrophilic carrier and PEGylated product was also prepared. The prepared products were evaluated for various parameters, such as polymer interaction, saturation solubility study, and drug release studies. The drug release data were analyzed by fitting it into various kinetic models. RESULTS There is an improvement in the dissolution from 16% to 70% with solid dispersion technology. Higuchi model was found to be the best fit model. CONCLUSION Solid dispersion is the simple, efficient, and economic method to improve the dissolution of the poorly water-soluble drugs.
Enhancement of dissolution of Telmisartan through use of solid dispersion technique - surface solid dispersion.
Department of Pharmaceutics and Pharmaceutical Technology, Student and Faculty of Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology Education Campus Changa, Gujarat, India.
The present study was aimed to increase the solubility of the poorly water soluble drug Telmisartan by using Surface solid dispersion (SSD) made of polymers like Poloxamer 407, PEG 6000 by Solvent evaporation method. The drug was solubilized by surfactants and/or polymers then adsorbed onto the surface of extremely fine carriers to increase its surface area and to form the SSD which give the more Surface area for absorption of the drug. A 2(2) full factorial design was used to investigate for each carrier the joint influence of formulation variables: Amount of carrier and adsorbent. Saturation solubility studies shows the improvement in solubility of drug batch SSD 8 give more solubility improvement than the other batch, in-vitro dissolution of pure drug, physical mixtures and SSDs were carried out in that SSDs were found to be effective in increasing the dissolution rate of Telmisartan in form of SSD when compared to pure drug. Also FT-IR spectroscopy, differential scanning calorimetry and X-ray diffractometry studies were carried out in order to characterize the drug and Surface solid dispersion. Furthermore, both DSC and X-ray diffraction showed a decrease in the melting enthalpy and reduced drug crystallinity consequently in SSDs. However, infrared spectroscopy revealed no drug interactions with the carriers.
In vitro-in vivo evaluation of fast-dissolving tablets containing solid dispersion of pioglitazone hydrochloride.
Department of Pharmaceutics, Faculty of Pharmacy, Al-Ameen College of Pharmacy, Bangalore 560027, Karnataka, India.
Investigation of in vitro/in vivo behavior of fast-dissolving tablets containing solid dispersions of pioglitazone hydrochloride (PIO) is the focus of the present research work. The effect of various hydrophilic polymers on the aqueous solubility of PIO was studied. Poly vinyl pyrrolidine K 30 (PVPK 30) carrier was selected and solid dispersions were prepared by various methods. Evaluation of solid dispersion for percentage yield, drug content, solubility, and Fourier Transform Infrared-indicated kneading method was most appropriate. Furthermore, the dissolution studies exhibited an enhancement in drug dissolution. One-way ANOVA of in vitro data suggested that there was significant (P ≤ 0.05) difference in dissolution profile of PIO solid dispersion when compared with pure drug and commercial product. Infrared spectroscopy, differential scanning calorimetry, and powder X-ray diffraction performed on solid dispersion indicated lack of physicochemical interaction between the drug and the carrier. The selected formulation is compressed into fast-dissolving tablets which were further evaluated for tablet properties and in vitro drug release. In vivo studies of pure drug, selected formulation, and marketed product were carried out in male Wistar rats and pharmacokinetic parameters were calculated using Kinetica software 2000. The best formulation has shown T(max) of 1 hour which was highly significant (P < 0.01) when compared with pure drug and marketed formulation. Therefore, the solid dispersions prepared by kneading method using PVPK 30 as hydrophilic carrier can be successfully used for improvement of dissolution of PIO and resulted in faster onset of action as indicated by in vivo studies.
Department of Pharmaceutics, Faculty of Pharmacy, Umm Al Qura University, Saudi Arabia.
Domperidone is a highly water insoluble drug exhibiting poor dissolution pattern. The purpose of this work was to increase the dissolution rate of Domperidone by formation of solid dispersion with different water soluble carriers. Binary systems of Domperidone were prepared with polyvinyl pyrrolidone k-30 (PVP), poloxamer 188 (P188) and polyethylene glycol 6000 (PEG 6000) at different weight ratios using the solvent evaporation method, physical mixtures of the same systems were also used. The effect of the method of preparation was also investigated by preparing some selected formulations using melting method. As P188 is known to inhibit CYP3A4 enzyme which is responsible for hepatic metabolism of many drugs including Domperidone, the effect of incorporation of PVP or PEG 6000 as ternary component to P188 solid dispersion on dissolution rate was also investigated. Formulations were characterized by Fourier transform infrared (FTIR) and Differential scanning calorimetry (DSC). Drug content uniformity and dissolution rate were studied. Solid dispersions showed a better dissolution compared to the pure drug and physical mixtures, with PVP showing the highest dissolution efficiency. As indicated from DSC data, Domperidone was in the amorphous form, which confirmed the better dissolution rate of solid dispersions. Some ternary P188 combinations showed a better enhancement in drug dissolution compared to the optimized P188 binary system. This would present a potential of increasing oral bioavailability of Domperidone by increasing its dissolution rate and by inhibiting its pre-systemic metabolism by the presence of P188.
J Pharm Biomed Anal. 2012 Jul 31;: 22898722
Comparative analysis of zaleplon complexation with cyclodextrins and hydrophilic polymers in solution and in solid state.
Department of Analytical Chemistry, Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia.
The aim of this work was to investigate the potential synergistic effect of water-soluble polymers (hypromellose, HPMC and polyvinylpyrrolidone, PVP) on zaleplon (ZAL) complexation with parent β-cyclodextrin (βCD) and its randomly methylated derivative (RAMEB) in solution and in solid state. The addition of HPMC to the complexation medium improved ZAL complexation and solubilization with RAMEB (K(ZAL/RAMEB)=156±5M(-1) and K(ZAL/RAMEB/HPMC)=189±8M(-1); p<0.01), while such effect was not observed for βCD (K(ZAL/βCD)=112±2M(-1) and K(ZAL/βCD/HPMC)=119±8M(-1); p>0.05). Although PVP increased the ZAL aqueous solubility from 0.22 to 0.27mg/mL, it did not show any synergistic effects on ZAL solubilization with the cyclodextrins tested. Binary and ternary systems of ZAL with βCD, RAMEB and HPMC were prepared by spray-drying. Differential scanning calorimetry, X-ray powder diffraction and scanning electron microscopy demonstrated a partial ZAL amorphization in spray-dried binary and ternary systems with βCD, while the drug was completely amorphous in all samples with RAMEB. Furthermore, inclusion complex formation in all systems prepared was confirmed by solid-state NMR spectroscopy. The in vitro dissolution rate followed the rank order ZAL/RAMEB/HPMC>ZAL/RAMEB=ZAL/βCD/HPMC>ZAL/βCD≫ZAL, clearly demonstrating the superior performance of RAMEB on ZAL complexation in the solid state and its synergistic effect with HPMC on drug solubility. Surprisingly, when loaded into tablets made with insoluble microcrystalline cellulose, RAMEB complexes had no positive effect on drug dissolution, because HPMC and RAMEB acted as a binders inside the tablets, prolonging their disintegration. Oppositely, the formulation with mannitol, a soluble excipient, containing a ternary RAMEB system, released the complete drug-dose in only 5min, clearly demonstrating its suitability for the development of immediate-release oral formulation of ZAL.
Maliba Pharmacy College, Bardoli Mahuva road, Dist. Surat, Gujarat, India -394 350. firstname.lastname@example.org.
The present study was carried out with a view to enhance dissolution rate of poorly water-soluble drug glipizide (GZ)(BCS class II) using polyethylene glycol (PEG) 6000, PEG 8000 and poloxamer (PXM) 188 as carriers. Solid dispersions (SDs) were prepared by melting method using different ratios of glipizide to carriers. Phase solubility study was conducted to evaluate the effect of carrier on aqueous solubility of glipizide. SD was optimized by drug content estimation and in vitro dissolution study and optimised SD was subjected to bulk characterization, Scanning electron microscopy (SEM), Fourier transformation infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC) and X-ray diffraction study (XRD). Preclinical study was performed in mice to study the decrease in blood glucose level from prepared SD compared with pure drug. Due to high solubility and drug release, PXM 188 in weight ratio of 1:2 was optimized. Decrease in blood glucose level in mice from SD was significantly higher (p < 0.05) compared to pure glipizide. Thus, solid dispersion technique can be successfully used for the improvement of the dissolution profile of GZ.
School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, United Kingdom.
We have investigated the dissolution mechanisms of spray-dried amorphous solid dispersions of the poorly water-soluble drug felodipine and the water-soluble polymer copovidone using a new combined spectrophotometric and magnetic resonance imaging technique and a mathematical modelling approach. Studies of the dissolution rates of both uncompacted and compacted solid dispersions revealed that compaction leads to a significant decrease in the rate and extent of dissolution and a strong dependence on drug loading, especially for the uncompacted samples. Low drug-loaded compacts [5% and 15%(w/w) felodipine] eroded with linear kinetics at identical rates, pointing to matrix control, whereas for compacts containing a higher proportion of felodipine (≥ 30%, w/w), dissolution performance was dominated by the drug. In these cases, felodipine concentrations were extremely low and the compact swelled rather than eroded. We have developed a mathematical population balance framework to model the processes of particle release, dissolution and crystal growth. This was found to accurately describe the bell-shaped dissolution profiles observed for the compacts containing a low felodipine loading. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:2798-2810, 2012.
Acta Pol Pharm. ;69 (2):299-308 22568045
An improvement in physicochemical properties of carvedilol through spherically agglomerated solid dispersions with PVP K30.
Sudhakarrao Naik Institute of Pharmacy, Pusad-445204, Dist. Yavatmal, Maharashtra, India. email@example.com
Spherically agglomerated solid dispersions of carvedilol (CAR) were prepared with polyvinyl-pyrrolidone (PVP) using acetone, water and dichloromethane as solvent, non-solvent and bridging liquid, respectively. The prepared agglomerates were evaluated for its percentage yield, drug content, morphology, thermal behavior, micromeritic properties, aqueous solubility and in vitro drug release. Differential scanning calorimetric and powder X-ray diffraction studies confirm that formulation process altered the crystalline nature of carvedilol. The recrystallized agglomerates exhibited significant increase (p < 0.05) in micromeritic properties than untreated carvedilol. Solubility and in vitro drug release studies indicated that the spherical agglomerates showed significant increase (p < 0.05) in solubility and dissolution rate than pure carvedilol alone.
Drug Dev Ind Pharm. 2012 Apr 20;: 22519663
Investigation for the amorphous state of ER-34122, a dual 5-lipoxygenase/cyclooxygenase inhibitor with poor aqueous solubility, in HPMC solid dispersion prepared by the solvent evaporation method.
Analytical Research, CMC Japan, Pharmaceutical Science & Technology Core Function Unit, Eisai Product Creation Systems, Eisai Co., Ltd., Tokodai, Tsukuba, Ibaraki , Japan.
ER-34122, a poorly water-soluble dual 5-lipoxygenase/cyclooxygenase inhibitor, exists as a crystalline form. According to an Oak Ridge thermal ellipsoid plot drawing, carbonyl oxygen O (5) makes an intermolecular hydrogen bond with the hydrogen bonded to N (3) in the crystal structure. The FTIR and the solid-state (13)C NMR spectra suggest that the network is spread out in the amorphous state and the hydrogen bonding gets weaker than that in the crystalline phase, because the carbonyl signals significantly shift in both spectra. When amorphous ER-34122 was heated, crystallization occurred at around 140°C. Similar crystallization happened in the solid dispersion; however, the degree of crystallization was much lower than that observed in the pure amorphous material. Also, the DSC thermogram of the solid dispersion did not show any exothermic peaks implying crystallization. The heat of fusion (ΔH(f)) determined in the pure amorphous material was nearly equal to that for the crystalline form, whereas the ΔH(f) value obtained in the solid dispersion was less than a third of them. These data prove that crystallization of the amorphous form is dramatically restrained in the solid dispersion system. The carbonyl wavenumber shifts in the FTIR spectra indicate that the average hydrogen bond in the solid dispersion is lower than that in the pure amorphous material. Therefore, HPMC will suppress formation of the intermolecular network observed in ER-34122 crystal and preserve the amorphous state, which is thermodynamically less stable, in the solid dispersed system.