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Solid Dispersion (solid + dispersion)
Selected AbstractsDrug,polymer interaction and its significance on the physical stability of nifedipine amorphous dispersion in microparticles of an ammonio methacrylate copolymer and ethylcellulose binary blendJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2008Jingjun Huang Abstract Using spectroscopic and thermal analysis, this study investigated drug,polymer interaction and its significance on the physical stability of drug amorphous dispersion in microparticles of an ammonio polymethacrylate copolymer (Eudragit RL®) (RL) and ethylcellulose (EC) binary blend (RL/EC,=,2:1 w/w) prepared for use in controlled release of poorly water-soluble drugs. Solid dispersion of the model drug, nifedipine in the microparticles could be described as an ideal amorphous mixture for drug loadings up to 11% w/w. The antiplasticizing effect of the polymer blend was indicated by a significant increase in the glass transition point from ,50°C for the amorphous nifedipine to ,115°C for its solid solution. Moreover, shifts in infrared vibration wavenumber of nifedipine carbonyl and amine groups suggested that the hydrogen bonds (H-bonds) originally formed among nifedipine molecules were broken and replaced by those formed between nifedipine and polymers in the microparticles. Further infrared analysis on nifedipine amorphous dispersions with a single polymer, namely RL or EC, confirmed the proposed hydrogen-bonding interactions; and their stability study results suggested that both antiplasticizing effects and hydrogen bonding of EC and RL with nifedipine might be responsible for the physical stability of the microparticles of nifedipine amorphous dispersion with a RL/EC binary blend. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:251,262, 2008 [source] Effect of characteristics of compounds on maintenance of an amorphous state in solid dispersion with crospovidoneJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 6 2007Yusuke Shibata Abstract Solid dispersion (SD) of indomethacin with crospovidone (CrosPVP) shows useful characteristics for preparation of dosage forms. This study aimed to determine the types of drugs that could adopt a stable amorphous form in SD. Twenty compounds with various melting points (70,218°C), molecular weights (135,504) and functional groups (amide, amino, carbonyl, hydroxyl, ketone etc.) were prepared in SD with CrosPVP. The CrosPVP SDs were prepared using a mechanical mixing and heating method. Melting point and molecular weight were found to have no influence on the ability of a compound to maintain an amorphous state in SD. All compounds containing hydrogen-bond-donor functional groups existed in an amorphous state in SD for at least 6 months. Infrared spectra suggested an interaction between the functional groups of these compounds and amide carbonyl group of CrosPVP. Compounds without hydrogen-bond-donor groups could not maintain an amorphous state and underwent recrystallization within 1 month. It was suggested that the presence of a hydrogen-bond-donor functional group in a compound is an important factor affecting the stable formation of SD with CrosPVP, which contains a hydrogen-bond acceptor. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96:1537,1547, 2007 [source] Solid dispersion of rutaecarpine improved its antihypertensive effect in spontaneously hypertensive ratsBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 9 2008Jin-Song Ding Abstract It was reported previously that rutaecarpine produced a hypotensive effect in phenol-induced and 2-kidney, 1-clip hypertensive rats. However, the same dose of crude rutaecarpine did not produce significant hypotensive effects when applied to spontaneously hypertensive rats (SHR). In the present study, a different dose of rutaecarpine solid dispersion was administered intragastrically to SHR. The systolic blood pressure was monitored by the tail-cuff method with an electro-sphygmomanometer. The plasma concentration of rutaecarpine, calcitonin gene-related peptide (CGRP) and the mRNA levels of CGRP in dorsal root ganglion were determined. The results showed that administration of the solid dispersion significantly increased the blood concentration of rutaecarpine, accompanied by significant hypotensive effects in SHR in a dose-dependent manner. The levels of plasma CGRP were also elevated significantly, concomitantly with the increased mRNA levels in the dorsal root ganglion in a dose-dependent manner. It was concluded that a change of the dosage from the crude drug to solid dispersion could improve significantly the efficiency of rutaecarpine absorption and increase its plasma concentration. The anti-hypertensive effect exerted by rutaecarpine solid dispersion in SHR is mediated by CGRP. Copyright © 2008 John Wiley & Sons, Ltd. [source] Improving the dissolution and oral bioavailability of the poorly water-soluble drug aloe-emodin by solid dispersion with polyethylene glycol 6000DRUG DEVELOPMENT RESEARCH, Issue 5 2009Hao-gang Duan Abstract Solid dispersions (SDs) of aloe-emodin (AE) and polyethylene glycol 6000 (PEG6000) with different drug loadings were prepared, characterized by scanning electron microscopy (SEM) and differential scanning calorimetry (DSC) and evaluated for solubility and in vitro release. The oral bioavailability of AE from SD in rats was compared with the crystalline drug. Plasma concentrations of AE were determined by HPLC. After administration of crystalline AE (35,mg·kg,1) in rats, the AUC0-600 and Cmax were 393.6±77.1,mg·min·l,1 and 1.87±0.30,mg·l,1, respectively. For the PEG6000 SD of AE, AUC0-600 and Cmax were boosted to 1310.5±111.9,mg·min·l,1 and 5.86±0.47,mg·l,1, respectively. The results indicated that the oral bioavailability of AE was increased significantly. Simultaneously, the Tmax value of AE for AE crystalline was decreased from 75.6±17.3,min to 44.8±14.8,min for SD. The earlier Tmax for AE from SD indicated the higher extent of absorption for SD due to their improved dissolution rate in rat intestine. This SD approach can therefore be used to enhanced dissolution and bioavailability for poorly water-soluble drugs. Drug Dev Res, 2009. © 2009 Wiley-Liss, Inc. [source] A solid-state approach to enable early development compounds: Selection and animal bioavailability studies of an itraconazole amorphous solid dispersionJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 9 2010David Engers Abstract A solid-state approach to enable compounds in preclinical development is used by identifying an amorphous solid dispersion in a simple formulation to increase bioavailability. Itraconazole (ITZ) was chosen as a model crystalline compound displaying poor aqueous solubility and low bioavailability. Solid dispersions were prepared with different polymers (PVP K-12, K29/32, K90; PVP VA S-630; HPMC-P 55; and HPMC-AS HG) at varied concentrations (1:5, 1:2, 2:1, 5:1 by weight) using two preparation methods (evaporation and freeze drying). Physical characterization and stability data were collected to examine recommended storage, handling, and manufacturing conditions. Based on generated data, a 1:2 (w/w) ITZ/HPMC-P dispersion was selected for further characterization, testing, and scale-up. Thermal data and computational analysis suggest that it is a possible solid nanosuspension. The dispersion was successfully scaled using spray drying, with the materials exhibiting similar physical properties as the screening samples. A simple formulation of 1:2 (w/w) ITZ/HPMC-P dispersion in a capsule was compared to crystalline ITZ in a capsule in a dog bioavailability study, with the dispersion being significantly more bioavailable. This study demonstrated the utility of using an amorphous solid form with desirable physical properties to significantly improve bioavailability and provides a viable strategy for evaluating early drug candidates. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:3901,3922, 2010 [source] Improving the dissolution and oral bioavailability of the poorly water-soluble drug aloe-emodin by solid dispersion with polyethylene glycol 6000DRUG DEVELOPMENT RESEARCH, Issue 5 2009Hao-gang Duan Abstract Solid dispersions (SDs) of aloe-emodin (AE) and polyethylene glycol 6000 (PEG6000) with different drug loadings were prepared, characterized by scanning electron microscopy (SEM) and differential scanning calorimetry (DSC) and evaluated for solubility and in vitro release. The oral bioavailability of AE from SD in rats was compared with the crystalline drug. Plasma concentrations of AE were determined by HPLC. After administration of crystalline AE (35,mg·kg,1) in rats, the AUC0-600 and Cmax were 393.6±77.1,mg·min·l,1 and 1.87±0.30,mg·l,1, respectively. For the PEG6000 SD of AE, AUC0-600 and Cmax were boosted to 1310.5±111.9,mg·min·l,1 and 5.86±0.47,mg·l,1, respectively. The results indicated that the oral bioavailability of AE was increased significantly. Simultaneously, the Tmax value of AE for AE crystalline was decreased from 75.6±17.3,min to 44.8±14.8,min for SD. The earlier Tmax for AE from SD indicated the higher extent of absorption for SD due to their improved dissolution rate in rat intestine. This SD approach can therefore be used to enhanced dissolution and bioavailability for poorly water-soluble drugs. Drug Dev Res, 2009. © 2009 Wiley-Liss, Inc. [source] A solid-state approach to enable early development compounds: Selection and animal bioavailability studies of an itraconazole amorphous solid dispersionJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 9 2010David Engers Abstract A solid-state approach to enable compounds in preclinical development is used by identifying an amorphous solid dispersion in a simple formulation to increase bioavailability. Itraconazole (ITZ) was chosen as a model crystalline compound displaying poor aqueous solubility and low bioavailability. Solid dispersions were prepared with different polymers (PVP K-12, K29/32, K90; PVP VA S-630; HPMC-P 55; and HPMC-AS HG) at varied concentrations (1:5, 1:2, 2:1, 5:1 by weight) using two preparation methods (evaporation and freeze drying). Physical characterization and stability data were collected to examine recommended storage, handling, and manufacturing conditions. Based on generated data, a 1:2 (w/w) ITZ/HPMC-P dispersion was selected for further characterization, testing, and scale-up. Thermal data and computational analysis suggest that it is a possible solid nanosuspension. The dispersion was successfully scaled using spray drying, with the materials exhibiting similar physical properties as the screening samples. A simple formulation of 1:2 (w/w) ITZ/HPMC-P dispersion in a capsule was compared to crystalline ITZ in a capsule in a dog bioavailability study, with the dispersion being significantly more bioavailable. This study demonstrated the utility of using an amorphous solid form with desirable physical properties to significantly improve bioavailability and provides a viable strategy for evaluating early drug candidates. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:3901,3922, 2010 [source] Drug,polymer solubility and miscibility: Stability consideration and practical challenges in amorphous solid dispersion developmentJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2010Feng Qian Abstract Drug,polymer solid dispersion has been demonstrated as a feasible approach to formulate poorly water-soluble drugs in the amorphous form, for the enhancement of dissolution rate and bioperformance. The solubility (for crystalline drug) and miscibility (for amorphous drug) in the polymer are directly related to the stabilization of amorphous drug against crystallization. Therefore, it is important for pharmaceutical scientists to rationally assess solubility and miscibility in order to select the optimal formulation (e.g., polymer type, drug loading, etc.) and recommend storage conditions, with respect to maximizing the physical stability. This commentary attempts to discuss the concepts and implications of the drug,polymer solubility and miscibility on the stabilization of solid dispersions, review recent literatures, and propose some practical strategies for the evaluation and development of such systems utilizing a working diagram. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:2941,2947, 2010 [source] Effect of temperature and moisture on the miscibility of amorphous dispersions of felodipine and poly(vinyl pyrrolidone)JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2010Patrick J. Marsac Abstract The physical stability of amorphous molecular level solid dispersions will be influenced by the miscibility of the components. The goal of this work was to understand the effects of temperature and relative humidity on the miscibility of a model amorphous solid dispersion. Infrared spectroscopy was used to evaluate drug,polymer hydrogen bonding interactions in amorphous solid dispersions of felodipine and poly(vinyl pyrrolidone) (PVP). Samples were analyzed under stressed conditions: high temperature and high relative humidity. The glass transition temperature (Tg) of select systems was studied using differential scanning calorimetry (DSC). Atomic force microscopy (AFM) and transmission electron microscopy (TEM) were used to further investigate moisture-induced changes in solid dispersions. Felodipine-PVP solid dispersions showed evidence of adhesive hydrogen bonding interactions at all compositions studied. The drug,polymer intermolecular interactions were weakened and/or less numerous on increasing the temperature, but persisted up to the melting temperature of the drug. Changes in the hydrogen bonding interactions were found to be reversible with changes in temperature. In contrast, the introduction of water into amorphous molecular level solid dispersions at room temperature irreversibly disrupted interactions between the drug and the polymer resulting in amorphous-amorphous phase separation followed by crystallization. DSC, AFM, and TEM results provided further evidence for the occurrence of moisture induced immiscibility. In conclusion, it appears that felodipine-PVP solid dispersions are susceptible to moisture-induced immiscibility when stored at a relative humidity ,75%. In contrast, the solid dispersions remained miscible on heating. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:169,185, 2010 [source] Anomalous properties of spray dried solid dispersionsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 12 2009Hisham Al-Obaidi Abstract The use of solid dispersions for oral dosage forms can increase the dissolution rate of poorly soluble drugs. Spray drying is one process that can be used to prepare solid dispersions. Spray dried solid dispersions of griseofulvin, poly[N -(2-hydroxypropyl)methacrylate] (PHPMA) and polyvinylpyrrolidone (PVP) were prepared from acetone and water. When methanol was substituted for water, the morphology, stability and dissolution properties of the solid dispersion changed dramatically. The glass transition temperature for the ternary solid dispersion (GF, PHPMA, and PVP) shifted from 83°C (acetone/water) to 103°C for the acetone/methanol system. These differences in the dispersions are thought to derive from conformational variations of the polymers in solution prior to spray drying. Both PHPMA and PVP formed globules in solution of a size range between 16 and 33 nm. The effect of drug and polymer concentration in solution (before spray drying) on the properties of the solid dispersion was studied. It was found that solid dispersions that were prepared using lower concentrations of drug and polymers in solutions resulted in the formation of particles that display a lower relaxation rate. This result supports the hypothesis that the polymer conformation may significantly change the properties of the solid dispersion. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4724,4737, 2009 [source] Effect of characteristics of compounds on maintenance of an amorphous state in solid dispersion with crospovidoneJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 6 2007Yusuke Shibata Abstract Solid dispersion (SD) of indomethacin with crospovidone (CrosPVP) shows useful characteristics for preparation of dosage forms. This study aimed to determine the types of drugs that could adopt a stable amorphous form in SD. Twenty compounds with various melting points (70,218°C), molecular weights (135,504) and functional groups (amide, amino, carbonyl, hydroxyl, ketone etc.) were prepared in SD with CrosPVP. The CrosPVP SDs were prepared using a mechanical mixing and heating method. Melting point and molecular weight were found to have no influence on the ability of a compound to maintain an amorphous state in SD. All compounds containing hydrogen-bond-donor functional groups existed in an amorphous state in SD for at least 6 months. Infrared spectra suggested an interaction between the functional groups of these compounds and amide carbonyl group of CrosPVP. Compounds without hydrogen-bond-donor groups could not maintain an amorphous state and underwent recrystallization within 1 month. It was suggested that the presence of a hydrogen-bond-donor functional group in a compound is an important factor affecting the stable formation of SD with CrosPVP, which contains a hydrogen-bond acceptor. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96:1537,1547, 2007 [source] The use of three different solid dispersion formulations,melt extrusion, film-coated beads, and a glass thermoplastic system,to improve the bioavailability of a novel microsomal triglyceride transfer protein inhibitorJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 5 2004Geert Verreck Abstract A bioavailable formulation for a water-insoluble microsomal triglyceride transfer protein inhibitor, R103757, was developed using solid dispersion technology. The need for an advanced formulation was tested in the dog by assessing the oral bioavailability of three generic concepts: a tablet (crystalline drug), a capsule (film-coated beads), and an oral solution. These screening studies steered further development in the direction of a solid dispersion. Three solid dispersion platforms were assessed: melt extrusion, film-coated beads, and a glass thermoplastic system. Thermal and spectrophotometric analysis revealed that no crystalline drug was present in any of the formulations. The dissolution profiles of the three dispersion systems showed that release was improved compared with the unmanipulated drug. In addition, stability studies confirmed the physical and chemical integrity of the formulation. A human clinical trial was performed to assess the pharmacokinetics of the three amorphous dispersions. Plasma levels were obtained after single oral administration in both the fasting and fed state. The study indicated that all three approaches improved the bioavailability of R103757 with the glass thermoplastic system providing the best performance. These studies point to the potential usefulness of solid dispersion approaches and expand the possible number of ways to implement these methodologies. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:1217,1228, 2004 [source] Improvement of dissolution and oral absorption of ER-34122, a poorly water-soluble dual 5-lipoxygenase/cyclooxygenase inhibitor with anti-inflammatory activity by preparing solid dispersionJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2002Ikuo Kushida Abstract Several formulation approaches were attempted to improve the dissolution and the oral absorption of ER-34122, which is a novel dual 5-lipoxygenase/cyclooxygenase inhibitor with potent anti-inflammatory activity. The solid dispersion of ER-34122 with hydroxypropylmethylcellulose (TC-5RW), which is an inert solid carrier, resulted in a significant improvement in the dissolution rate of ER-34122. The solid dispersion was prepared by a solvent evaporation method using ethanol and water. The solid-state characteristics of the solid dispersion, the corresponding physical mixture, and ER-34122 alone were investigated by X-ray powder diffraction, Fourier transform infrared spectroscopy (FTIR), and an automated controlled-atmosphere microbalance. The X-ray powder diffraction patterns suggest that the solid dispersion exists in a totally amorphous state and the others exist in a crystalline state. The FTIR spectra results suggest that ER-34122 can interact with TC-5RW through intermolecular hydrogen bonding in the solid dispersion. This interaction may cause a stabilization of ER-34122 in the higher-energy, faster-dissolving amorphous state. The dissolution rate of ER-34122 from the solid dispersion was significantly greater than that from the physical mixture or the pure drug. Furthermore, when orally administrated to beagle dogs, ER-34122 showed about a 100-fold increase in both maximum concentration (Cmax) and area under the curve of concentration versus time (AUC) compared with the pure drug. Consequently, it was determined that the solid dispersion technique with TC-5RW provides a promising way to increase the dissolution rate and the oral absorption of poorly water-soluble drugs such as ER-34122. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:258,266, 2002 [source] Cefuroxime axetil solid dispersions prepared using solution enhanced dispersion by supercritical fluidsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 12 2005Seoung Wook Jun Cefuroxime axetil (CA) solid dispersions with HPMC 2910/PVP K-30 were prepared using solution enhanced dispersion by supercritical fluids (SEDS) in an effort to increase the dissolution rate of poorly water-soluble drugs. Their physicochemical properties in solid state were characterized by differential scanning calorimeter (DSC), powder X-ray diffraction (PXRD), Fourier transform infrared spectrometry (FT-IR) and scanning electron microscopy. No endothermic and characteristic diffraction peaks corresponding to CA were observed for the solid dispersions in DSC and PXRD. FTIR analysis demonstrated the presence of intermolecular hydrogen bonds between CA and HPMC 2910/PVP K-30 in solid dispersions, resulting in the formation of amorphous or non-crystalline CA. Dissolution studies indicated that the dissolution rates were remarkably increased in solid dispersions compared with those in the physical mixture and drug alone. In conclusion, an amorphous or non-crystalline CA solid dispersion prepared using SEDS could be very useful for the formulation of solid dosage forms. [source] Solid dispersion of rutaecarpine improved its antihypertensive effect in spontaneously hypertensive ratsBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 9 2008Jin-Song Ding Abstract It was reported previously that rutaecarpine produced a hypotensive effect in phenol-induced and 2-kidney, 1-clip hypertensive rats. However, the same dose of crude rutaecarpine did not produce significant hypotensive effects when applied to spontaneously hypertensive rats (SHR). In the present study, a different dose of rutaecarpine solid dispersion was administered intragastrically to SHR. The systolic blood pressure was monitored by the tail-cuff method with an electro-sphygmomanometer. The plasma concentration of rutaecarpine, calcitonin gene-related peptide (CGRP) and the mRNA levels of CGRP in dorsal root ganglion were determined. The results showed that administration of the solid dispersion significantly increased the blood concentration of rutaecarpine, accompanied by significant hypotensive effects in SHR in a dose-dependent manner. The levels of plasma CGRP were also elevated significantly, concomitantly with the increased mRNA levels in the dorsal root ganglion in a dose-dependent manner. It was concluded that a change of the dosage from the crude drug to solid dispersion could improve significantly the efficiency of rutaecarpine absorption and increase its plasma concentration. The anti-hypertensive effect exerted by rutaecarpine solid dispersion in SHR is mediated by CGRP. Copyright © 2008 John Wiley & Sons, Ltd. [source] Solubility studies on valdecoxib in the presence of carriers, cosolvents, and surfactantsDRUG DEVELOPMENT RESEARCH, Issue 1 2004Kashappa Goud H. Desai Abstract Enhancement of the solubility of valdecoxib was examined using a series of hydrophilic carriers (mannitol, polyethylene glycol (PEG) 4000, PEG 6000, PEG 8000, and urea), surfactants (Tween-20, Tween-80, and sodium lauryl sulfate [SLS]) and cosolvents (ethanol, methanol, and glycerol) at 37°C. The solubility of valdecoxib could be enhanced significantly using PEG 4000 as a carrier, ethanol as cosolvent, and SLS as a surfactant. Because the solubility of valdecoxib increased dramatically in the presence of polyethylene glycols, these are suitable dispersing agents for preparing solid dispersions containing valdecoxib. Gibbs free energy (,G) values were all negative for all hydrophilic carriers tested, indicating the spontaneous nature of valdecoxib solubilisation. Among the cosolvents, ethanol exhibited higher solubilization potential than methanol and glycerol. As the dielectric constant of the cosolvent,water mixtures decreased, the solubility of valdecoxib increased. Finally, SLS exerted maximum solubilization of valdecoxib when compared to Tween-20 or Tween-80. The crystallinity of valdecoxib was explored by X-ray diffraction study and showed numerous crystalline peaks. Examination of surface morphology by scanning electron microscopy depicted a near spherical shape of valdecoxib with irregular surface characteristics. Drug Dev. Res. 62:41,48, 2004. © 2004 Wiley-Liss, Inc. [source] Drug,polymer solubility and miscibility: Stability consideration and practical challenges in amorphous solid dispersion developmentJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2010Feng Qian Abstract Drug,polymer solid dispersion has been demonstrated as a feasible approach to formulate poorly water-soluble drugs in the amorphous form, for the enhancement of dissolution rate and bioperformance. The solubility (for crystalline drug) and miscibility (for amorphous drug) in the polymer are directly related to the stabilization of amorphous drug against crystallization. Therefore, it is important for pharmaceutical scientists to rationally assess solubility and miscibility in order to select the optimal formulation (e.g., polymer type, drug loading, etc.) and recommend storage conditions, with respect to maximizing the physical stability. This commentary attempts to discuss the concepts and implications of the drug,polymer solubility and miscibility on the stabilization of solid dispersions, review recent literatures, and propose some practical strategies for the evaluation and development of such systems utilizing a working diagram. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:2941,2947, 2010 [source] Effect of temperature and moisture on the miscibility of amorphous dispersions of felodipine and poly(vinyl pyrrolidone)JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2010Patrick J. Marsac Abstract The physical stability of amorphous molecular level solid dispersions will be influenced by the miscibility of the components. The goal of this work was to understand the effects of temperature and relative humidity on the miscibility of a model amorphous solid dispersion. Infrared spectroscopy was used to evaluate drug,polymer hydrogen bonding interactions in amorphous solid dispersions of felodipine and poly(vinyl pyrrolidone) (PVP). Samples were analyzed under stressed conditions: high temperature and high relative humidity. The glass transition temperature (Tg) of select systems was studied using differential scanning calorimetry (DSC). Atomic force microscopy (AFM) and transmission electron microscopy (TEM) were used to further investigate moisture-induced changes in solid dispersions. Felodipine-PVP solid dispersions showed evidence of adhesive hydrogen bonding interactions at all compositions studied. The drug,polymer intermolecular interactions were weakened and/or less numerous on increasing the temperature, but persisted up to the melting temperature of the drug. Changes in the hydrogen bonding interactions were found to be reversible with changes in temperature. In contrast, the introduction of water into amorphous molecular level solid dispersions at room temperature irreversibly disrupted interactions between the drug and the polymer resulting in amorphous-amorphous phase separation followed by crystallization. DSC, AFM, and TEM results provided further evidence for the occurrence of moisture induced immiscibility. In conclusion, it appears that felodipine-PVP solid dispersions are susceptible to moisture-induced immiscibility when stored at a relative humidity ,75%. In contrast, the solid dispersions remained miscible on heating. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:169,185, 2010 [source] Anomalous properties of spray dried solid dispersionsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 12 2009Hisham Al-Obaidi Abstract The use of solid dispersions for oral dosage forms can increase the dissolution rate of poorly soluble drugs. Spray drying is one process that can be used to prepare solid dispersions. Spray dried solid dispersions of griseofulvin, poly[N -(2-hydroxypropyl)methacrylate] (PHPMA) and polyvinylpyrrolidone (PVP) were prepared from acetone and water. When methanol was substituted for water, the morphology, stability and dissolution properties of the solid dispersion changed dramatically. The glass transition temperature for the ternary solid dispersion (GF, PHPMA, and PVP) shifted from 83°C (acetone/water) to 103°C for the acetone/methanol system. These differences in the dispersions are thought to derive from conformational variations of the polymers in solution prior to spray drying. Both PHPMA and PVP formed globules in solution of a size range between 16 and 33 nm. The effect of drug and polymer concentration in solution (before spray drying) on the properties of the solid dispersion was studied. It was found that solid dispersions that were prepared using lower concentrations of drug and polymers in solutions resulted in the formation of particles that display a lower relaxation rate. This result supports the hypothesis that the polymer conformation may significantly change the properties of the solid dispersion. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4724,4737, 2009 [source] Review: physical chemistry of solid dispersionsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 12 2009Sandrien Janssens Abstract Objectives With poorly soluble drug candidates emerging in the drug discovery pipeline, the importance of the solid dispersion formulation approach is increasing. This strategy includes complete removal of drug crystallinity, and molecular dispersion of the poorly soluble compound in a hydrophilic polymeric carrier. The potential of this technique to increase oral absorption and hence bioavailability is enormous. Nevertheless, some issues have to be considered regarding thermodynamic instability, as well in supersaturated solutions that are formed upon dissolution as in the solid state. Key findings After a brief discussion on the historical background of solid dispersions and their current role in formulation, an overview will be given on the physical chemistry and stability of glass solutions as they form supersaturated solutions, and during their shelf life. Conclusions Thorough understanding of these aspects will elicit conscious evaluation of carrier properties and eventually facilitate rational excipient selection. Thus, full exploitation of the solid dispersion strategy may provide an appropriate answer to drug attrition due to low aqueous solubility in later stages of development. [source] Enhanced solubility and dissolution rate of lamotrigine by inclusion complexation and solid dispersion techniqueJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2008Vikram R. Shinde ABSTRACT The solid-state properties and dissolution behaviour of lamotrigine in its inclusion complex with ,-cyclodextrin (,CD) and solid dispersions with polyvinylpyrrolidone K30 (PVP K30) and polyethyl-eneglycol 6000 were investigated. The phase solubility profile of lamotrigine with ,CD was classified as AL -type, indicating formation of a 1:1 stoichiometry inclusion complex, with a stability constant of 369.96 ± 2.26 M,1. Solvent evaporation and kneading methods were used to prepare solid dispersions and inclusion complexes, respectively. The interaction of lamotrigine with these hydrophilic carriers was evaluated by powder X-ray diffractometry, Fourier transform infrared spectroscopy and differential scanning calorimetry. These studies revealed that the drug was no longer present in crystalline state but was converted to an amorphous form. Among the binary systems tested, PVP K30 (1:5) showed greatest enhancement of the solubility and dissolution of lamotrigine. [source] Cefuroxime axetil solid dispersions prepared using solution enhanced dispersion by supercritical fluidsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 12 2005Seoung Wook Jun Cefuroxime axetil (CA) solid dispersions with HPMC 2910/PVP K-30 were prepared using solution enhanced dispersion by supercritical fluids (SEDS) in an effort to increase the dissolution rate of poorly water-soluble drugs. Their physicochemical properties in solid state were characterized by differential scanning calorimeter (DSC), powder X-ray diffraction (PXRD), Fourier transform infrared spectrometry (FT-IR) and scanning electron microscopy. No endothermic and characteristic diffraction peaks corresponding to CA were observed for the solid dispersions in DSC and PXRD. FTIR analysis demonstrated the presence of intermolecular hydrogen bonds between CA and HPMC 2910/PVP K-30 in solid dispersions, resulting in the formation of amorphous or non-crystalline CA. Dissolution studies indicated that the dissolution rates were remarkably increased in solid dispersions compared with those in the physical mixture and drug alone. In conclusion, an amorphous or non-crystalline CA solid dispersion prepared using SEDS could be very useful for the formulation of solid dosage forms. [source] | ||||||||||