Salt Form (salt + form)

Distribution by Scientific Domains


Selected Abstracts


Evaluation of gastric toxicity of indomethacin acid, salt form and complexed forms with hydroxypropyl-,-cyclodextrin on Wistar rats: histopathologic analysis

FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 6 2009
A.C. Ribeiro-Rama
Abstract Indomethacin (IM) is a non-steroidal anti-inflammatory drug which inhibits prostaglandin biosynthesis. It is practically insoluble in water and has the capacity to induce gastric injury. Hydroxypropyl-,-cyclodextrin (HP-,-CD) is an alkylated derivative of ,-CD with the capacity to form inclusion complexes with suitable molecules. IM is considered to form partial inclusion complexes with HP-,-CD by enclosure of the p -chlorobenzoic part of the molecule in the cyclodextrin channel, reducing the adverse effects. The aim of this paper is to evaluate the gastric damage induced by the IM inclusion complex prepared by freeze-drying and spray-drying. A total of 135 Wistar rats weighing 224.4 ± 62.5 g were put into 10 groups. They were allowed free access to water but were maintained fasted for 18 h before the first administration until the end of the experiment. IM acid-form, IM trihydrated-sodium-salt and IM-HP-,-CD spray and freeze-dried, at normal and toxic doses, were administered through gastric cannula once/day for 3 days. Seventy-two hours after the first administration, the animals were sacrificed and the stomachs collected and prepared for morphological study by using the haematoxylin-eosin technique. Lesion indexes (rated 0/4) were developed and the type of injury was scored according to the severity of damage and the incidence of microscopic evidence of harm. Microscopic assessment demonstrated levels of injury with index one on 10,25%. The type of complexation method had different incidence but the same degree. The results show that IM inclusion complexation protects against gastric injury, reducing the incidence and the maximum degree of severity from 4 to 1, with a better performance of the spray-dried complex. [source]


Synthesis of processible doped polyaniline-polyacrylic acid composites

JOURNAL OF APPLIED POLYMER SCIENCE, Issue 2 2009
Bhavana Gupta
Abstract Processible composites of emeraldine salt form of polyaniline (PANI) with polyacrylic acid (PAA) are synthesized and studied for their structural, electrical, mechanical, thermal, and electrochemical properties. The processible conducting composites of various weight percentage from 20 wt % to 90 wt % (of PANI) have been prepared by mixing the PANI and PAA under vigorous stirring and sonication conditions. Self-standing films of electroactive homogeneous composites are obtained by solution casting method. A significant improvement in processibility, crystallinity, and thermal stability is observed in the composites; however, the electrical conductivity decreased remarkably as the percentage of PANI is decreased in the composites. The 60 wt % PANI-PAA composite showed crystalline structural property with orthorhombic crystal system and cell parameters as a = 5.93Ĺ, b = 7.57Ĺ, and c = 10.11Ĺ. The 60 wt % PANI-PAA composite also showed better thermal stability and highest capacitance amongst all the composites and used as an active material for development of electrochemical capacitors (parallel plate assembly). The processible composites based electrochemical capacitors using 0.5 M NaClO4 -Acetonitril electrolyte showed super capacitance with ease in fabrication and cost effectiveness in comparison to other similar materials based capacitors. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009 [source]


Process-induced phase transformation of berberine chloride hydrates

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2010
Henry H.Y. Tong
Abstract Berberine is a natural quaternary ammonium alkaloid used clinically in the chloride salt form for the treatment of diarrhea in many Asian countries. Although the hydrate formation of berberine chloride (BCl) is well documented, the associated mechanism and implications in pharmaceutical formulation have not been studied in detail. In this study, pure BCl dihydrate and BCl tetrahydrate were recrystallized from water and their phase transformation behaviors under defined conditions were investigated. Additionally, pharmacopoeial grade BCl material consisting predominantly of the dihydrate form was examined for potential phase changes when being subjected to a conventional wet granulation procedure for tablet production. Results from solubility measurements, thermal analysis, variable temperature-powder X-ray diffraction (VT-PXRD), and variable temperature-Fourier transform infrared spectroscopy (VT-FTIR) confirmed the solid-state interconversions between the tetrahydrate and dihydrate at 30,49°C and between the dihydrate and anhydrate at 70,87°C. Consistent with the observed phase changes of the two pure hydrates, wet massing of the pharmacopoeial grade BCl sample led to a thermodynamics-driven transition to the tetrahydrate form at room temperature while subsequent tray drying at 50°C caused a reversion back to the dihydrate form. The rate and extent of such hydrate conversion depended largely on the water activity of the granulated powder matrix, which in turn was governed by the particular excipients employed. The present findings have important implications in the regulation of the hydrate forms of BCl in the finished products using specific excipients. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1942,1954, 2010 [source]


Biowaiver monographs for immediate release solid oral dosage forms: Diclofenac sodium and diclofenac potassium,

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2009
B. Chuasuwan
Abstract Literature data are reviewed regarding the scientific advisability of allowing a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing either diclofenac potassium and diclofenac sodium. Within the biopharmaceutics classification system (BCS), diclofenac potassium and diclofenac sodium are each BCS class II active pharmaceutical ingredients (APIs). However, a biowaiver can be recommended for IR drug products of each salt form, due to their therapeutic use, therapeutic index, pharmacokinetic properties, potential for excipient interactions, and performance in reported BE/bioavailability (BA) studies, provided: (a) test and comparator contain the same diclofenac salt; (b) the dosage form of the test and comparator is identical; (c) the test product contains only excipients present in diclofenac drug products approved in ICH or associated countries in the same dosage form, for instance as presented in this paper; (d) test drug product and comparator dissolve 85% in 30 min or less in 900 mL buffer pH 6.8, using the paddle apparatus at 75 rpm or the basket apparatus at 100 rpm; and (e) test product and comparator show dissolution profile similarity in pH 1.2, 4.5, and 6.8. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:1206,1219, 2009 [source]


Effect of chloride ion on dissolution of different salt forms of haloperidol, a model basic drug

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 10 2005
Shoufeng Li
Abstract The effect of chloride ion (Cl,) on dissolution rates of hydrochloride, mesylate (methanesulfonate) and phosphate salt forms of a model drug, haloperidol, was investigated. The dissolution rates of the salts in 0.01M HCl from rotating disks followed the order of mesylate,,,phosphate,>,hydrochloride. With additional chloride ion, a decrease in dissolution rate of the hydrochloride salt was observed due to the common ion effect. Dissolution rates of mesylate and phosphate salts also decreased due to their conversion to the HCl salt form on the surfaces of dissolving disks, however, the dissolution rates of mesylate and phosphate salts under identical chloride ion concentrations were still higher than that of the HCl salt. In powder dissolution studies, it was observed that kinetics of nonhydrochloride-to-hydrochloride salt conversion play a major role in dissolution; the mesylate dissolved completely (<5 min) before its dissolution rate could be impeded by its conversion to the hydrochloride salt form. Therefore, despite the potential for conversion to a hydrochloride salt form, certain nonhydrochloride salt forms may still be preferred for dosage form development due to kinetic advantages during dissolution, such as higher apparent dissolution rate of a nonhydrochloride salt before it could completely convert to the hydrochloride form. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 94:2224,2231, 2005 [source]


Sulfonated naphthalene dianhydride based polyimide copolymers for proton-exchange-membrane fuel cells.

JOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 4 2004

Abstract A novel sulfonated diamine, 3,3,-disulfonic acid-bis[4-(3-aminophenoxy)phenyl]sulfone (SA-DADPS), was prepared from m -aminophenol and disodium-3,3,-disulfonate-4,4,-dichlorodiphenylsulfone. The conditions necessary to synthesize and purify SA-DADPS in high yields were investigated in some detail. This disulfonated aromatic diamine, containing ether and sulfone linkages, was used to prepare N -methyl-2-pyrrolidinone-soluble, six-membered ring polyimide copolymers containing pendent sulfonic acid groups by a catalyzed one-step high-temperature polycondensation in m -cresol. These materials showed much improved hydrolytic stability with respect to phthalimides. High-molecular-weight film-forming statistical copolymers with controlled degrees of disulfonation were prepared through variations in the stoichiometric ratio of disulfonated diamine (SA-DADPS) in its soluble triethylamine salt form to several unsulfonated diamines. Three unsulfonated diamines, bis[4-(3-aminophenoxy)phenyl] sulfone, 4,4,-oxydianiline, and 1,3-phenylenediamine, were used to prepare the copolymers. The characterization of the copolymers by 1H NMR, Fourier transform infrared, ion-exchange capacity, and thermogravimetric analysis demonstrated that SA-DADPS was quantitatively incorporated into the copolymers. Solution-cast films of the sulfonated copolymers were prepared and afforded tough, ductile membranes with high glass-transition temperatures. Methods were developed to acidify the triethylammonium salt membranes into their disulfonic acid form, this being necessary for proton conduction in a fuel cell. The synthesis and characterization of these materials are described in this article. Future articles will describe the performance of these copolymers as proton-exchange membranes in hydrogen/air and direct methanol fuel cells. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 862,874, 2004 [source]


Growth of the vacuoleless mutant of Tetrahymena thermophila NP1 in phytate

THE JOURNAL OF EUKARYOTIC MICROBIOLOGY, Issue 2 2005
SAMANTHA WEBB
Phytate, the salt form of phytic acid, is the major store of phosphate in seeds and grain. Since non-ruminant farm animals poorly digest phytate, it is also a source of environmental phosphate contamination in agricultural areas. We are using Tetrahymena, a ciliated protist with multiple routes for nutrient assimilation, as a model to investigate the contribution of heterotrophic protists to the environmental cycling of phosphate from phytate. This ciliate has the ability to grow on phytate as the sole phosphate source (Ziemkiewicz, H. T., Johnson, M. D. & Smith-Somerville, H. E. 2002. J. Eukaryot. Microbiol., 49:428). Tetrahymena thermophila NP1, a temperature-sensitive vacuoleless mutant (ATCC #50202), provides a way to separate membrane transport from uptake through phagosomes, and to assess the importance of each mechanism. This cell grows equally well at the permissive and non-permissive temperatures with either phytate or inorganic phosphate as the phosphate source. Our results demonstrate that phagosomes are not required to use the phosphate from phytate. [source]


The assessment of human regional drug absorption of free acid and sodium salt forms of Acipimox, in healthy volunteers, to direct modified release formulation strategy

BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 9 2009
Rajeev Menon
Abstract Acipimox is an analog of nicotinic acid and is indicated for the treatment of dyslipidemia. It is also believed to improve glucose control by enhancing insulin sensitivity. The purpose of this study was to direct modified release (MR) formulation strategy by comparing the bioavailability of two forms of acipimox (free acid and sodium salt) from the distal small bowel (DSB) and colon with an immediate release formulation. Two parallel groups of healthy volunteers completed an open label, non-randomized, three-way crossover study. The rate and extent of acipimox absorption was highest following administration of the immediate release capsules, and was not influenced by the form of the drug administered. Following administration to the DSB, the relative bioavailability was approximately 52% and 30% for the salt form and free acid form, respectively. Following administration to the colon, the extent of absorption was further reduced. The data indicate that bioavailability from the DSB was limited by the solubility of the drug coupled with an absorption window, whilst absorption from the colon was limited by permeability. The study provided detailed information to support and guide the formulation strategy for a MR form of acipimox, which may improve the treatment of adult patients with type II diabetes and dyslipidemia. Copyright © 2009 John Wiley & Sons, Ltd. [source]


Pharmacokinetics of SB-247083, a potent and selective endothelinA receptor antagonist, in the rat, dog, and monkey

BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 8 2002
Keith W. Ward
Abstract The endothelins (ET) are among the most potent vasoconstrictors identified to date, and have been implicated in such diseases as renal failure, pulmonary hypertension, atherosclerosis, and congestive heart failure. There is currently interest in developing selective antagonists of the ET-A subtype receptor, and one such antagonist is SB-247083 ((E)-[1-butyl-5-[2-(2-carboxyphenyl) methoxy-4-chlorophenyl]-1H-pyrazole-4-yl]-2-[5-methoxydihydrobenzofuran-6-yl]methyl]-2-propionic acid). This investigation was conducted to evaluate the preclinical pharmacokinetics of SB-247083. Clearance of SB-247083 was low to moderate in the rat and monkey, and high in the dog. Oral bioavailability of SB-247083 administered as a solid formulation of the free acid was 24% in the rat, but low in the dog (4%) and the monkey (2%). An extensive in vitro salt form and formulation screen resulted in the identification of a formulation containing the monoarginyl salt with improved dissolution properties. This formulation provided a 2- to 4-fold increase in oral bioavailability in each of the preclinical species. In the dog, this improvement was reversed by the pre-administration of 0.1 N HCl to normalize the achlorhydric fasting dog stomach. These data show that SB-247083 may have suitable drug properties for progression in development. Copyright © 2002 John Wiley & Sons, Ltd. [source]


Role of the Preparation Procedure in the Formation of Spherical and Monodisperse Surfactant/Polyelectrolyte Complexes

CHEMISTRY - A EUROPEAN JOURNAL, Issue 21 2007
Yuxia Luan Dr.
Abstract Complexes formed by a double-tail cationic surfactant, didodecyldimethyl ammonium bromide, and an anionic polyelectrolyte, an alternating copolymer of poly(styrene-alt-maleic acid) in its sodium salt form, were investigated with respect to variation in the charge ratio (x) between the polyelectrolyte negative charges and the surfactant positive charges. The morphology and microstructure of the complexes were studied by light microscopy and small-angle X-ray scattering for different preparation conditions. Independent of the sample preparation procedure and the charge ratio x, the X-ray results show that the microscopic structure of the complexes is a condensed lamellar phase. By contrast, the morphology of the complexes changes dramatically with the preparation procedure. The complexes formed by mixing a surfactant solution and a polyelectrolyte solution strongly depend on x and are always extremely heterogeneous in size and shape. Surprisingly, we show that, when the two solutions interdiffuse slowly, spherical complexes of micrometric and rather uniform size are systematically obtained, independently on the initial relative amount of surfactant and polyelectrolyte. The mechanism for the formation of these peculiar complexes is discussed. [source]


Combined use of crystalline salt forms and precipitation inhibitors to improve oral absorption of celecoxib from solid oral formulations

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 10 2007
Héctor R. Guzmán
Abstract Biopharmaceutical evaluation of crystalline celecoxib salts in novel solid formulations, which were designed to simultaneously facilitate dissolution and inhibit precipitation in vitro, showed fast and complete absorption in beagle dogs at doses up to 7.5 mg/kg orally. In contrast, 5 mg/kg celecoxib in the form of Celebrex® showed approximately 40% absolute bioavailability in a cross-over experiment. An in vitro,in vivo correlation was observed in dog, and a threshold level of in vitro dissolution needed to maximize in vivo performance was highlighted. Oral bioavailability was limited in the absence of excipient combinations that delayed precipitation of celecoxib free acid as the salt neutralized in the GI fluid. Formulations of crystal forms having high energy (a ,spring'), thus transiently increasing solubility in aqueous solution relative to the free acid, combined with excipients functioning as precipitation inhibitors (,parachutes') were shown to provide both enhanced dissolution and high oral bioavailability. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 2686,2702, 2007 [source]


Microenvironmental pH modulation in solid dosage forms

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 5 2007
Sherif I. Farag Badawy
Abstract There are many reports in the literature referring to the effect of ,microenvironmental pH' on solid dosage form performance, particularly stability and dissolution profiles. Several techniques have been proposed for the measurement of the microenvironmental pH. Those techniques use certain assumptions and approximations and many of them employ a solution calibration curve of a probe to predict hydrogen ion activity in a substantially dry solid. Despite the limitation of the methodology, it is clear from the literature that microenvironmental pH has a significant impact on stability of compounds which demonstrate pH dependent stability in solution. Degradation kinetics of such compounds, and in some cases degradation profile as well, are dependent on the microenvironmental pH of the solid. Modulation of the microenvironmental pH through the use of pH modifiers can hence prove to be a very effective tool in maximizing solid dosage form stability. Judicial selection of the appropriate pH modifier, its concentration and the manufacturing process used to incorporate the pH modifier is necessary to enhance stability. Control of microenvironmental pH to maximize stability can be achieved without the use of pH modifier in some cases if an appropriate counter ion is used to provide an inherently optimal pH for the salt. Microenvironmental pH modulation was also shown to control the dissolution profile of both immediate and controlled release dosage forms of compounds with pH dependent solubility. The pH modifiers have been used in conjunction with high energy or salt forms in immediate release formulations to minimize the precipitation of the less soluble free form during initial dissolution. Additionally, pH modifiers were utilized in controlled release dosage forms of weakly basic drugs which exhibit diminished release in dissolution media with high pH. The incorporation of acidic pH modifiers in the controlled release formulation increases the solubility of the basic drug even as the high pH dissolution medium enters into the dosage form hence increasing drug release rate. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 948,959, 2007 [source]


Effect of chloride ion on dissolution of different salt forms of haloperidol, a model basic drug

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 10 2005
Shoufeng Li
Abstract The effect of chloride ion (Cl,) on dissolution rates of hydrochloride, mesylate (methanesulfonate) and phosphate salt forms of a model drug, haloperidol, was investigated. The dissolution rates of the salts in 0.01M HCl from rotating disks followed the order of mesylate,,,phosphate,>,hydrochloride. With additional chloride ion, a decrease in dissolution rate of the hydrochloride salt was observed due to the common ion effect. Dissolution rates of mesylate and phosphate salts also decreased due to their conversion to the HCl salt form on the surfaces of dissolving disks, however, the dissolution rates of mesylate and phosphate salts under identical chloride ion concentrations were still higher than that of the HCl salt. In powder dissolution studies, it was observed that kinetics of nonhydrochloride-to-hydrochloride salt conversion play a major role in dissolution; the mesylate dissolved completely (<5 min) before its dissolution rate could be impeded by its conversion to the hydrochloride salt form. Therefore, despite the potential for conversion to a hydrochloride salt form, certain nonhydrochloride salt forms may still be preferred for dosage form development due to kinetic advantages during dissolution, such as higher apparent dissolution rate of a nonhydrochloride salt before it could completely convert to the hydrochloride form. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 94:2224,2231, 2005 [source]


Development of a nanofiltration process to improve the stability of a novel anti-MRSA carbapenem drug candidate

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2002
V. Antonucci
Abstract The benzenesulfonate salt of an anti-methicillin-resistant Staphylococcus aureus carbapenem antibiotic studied is a crystalline, nonhygroscopic powder which is stable at room temperature, making it an ideal compound for long-term storage. However, the limited aqueous solubility of this salt prohibits parenteral administration. Conversely, the chloride salt of this carbapenem demonstrates opposing characteristics; it is quantitatively soluble in water, however is amorphous and subject to significant hydrolytic degradation in the solid state. Given two such extreme alternatives for pharmaceutical salt selection, a common approach taken is to develop the bioavailable salt and devise manufacturing and storage conditions that minimize degradation. This report describes a different approach to this manufacturing dilemma via the application of a simple and efficient nanofiltration process to convert the benzenesulfonate salt (storage entity) to the chloride salt (formulated drug product). Such an approach combines the positive attributes of these two salt forms into a single scalable process that reduces processing cycle times via elimination of redundant unit operations, increases the flexibility in manufacturing schedule, and improves overall product quality. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91: 923,932, 2002 [source]


The assessment of human regional drug absorption of free acid and sodium salt forms of Acipimox, in healthy volunteers, to direct modified release formulation strategy

BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 9 2009
Rajeev Menon
Abstract Acipimox is an analog of nicotinic acid and is indicated for the treatment of dyslipidemia. It is also believed to improve glucose control by enhancing insulin sensitivity. The purpose of this study was to direct modified release (MR) formulation strategy by comparing the bioavailability of two forms of acipimox (free acid and sodium salt) from the distal small bowel (DSB) and colon with an immediate release formulation. Two parallel groups of healthy volunteers completed an open label, non-randomized, three-way crossover study. The rate and extent of acipimox absorption was highest following administration of the immediate release capsules, and was not influenced by the form of the drug administered. Following administration to the DSB, the relative bioavailability was approximately 52% and 30% for the salt form and free acid form, respectively. Following administration to the colon, the extent of absorption was further reduced. The data indicate that bioavailability from the DSB was limited by the solubility of the drug coupled with an absorption window, whilst absorption from the colon was limited by permeability. The study provided detailed information to support and guide the formulation strategy for a MR form of acipimox, which may improve the treatment of adult patients with type II diabetes and dyslipidemia. Copyright © 2009 John Wiley & Sons, Ltd. [source]