- An investigation into the solid-state properties and dissolution profile of spray dried ternary amorphous solid dispersions: A rational step towards the design and development of multi-component amorphous system. [Journal Article]
- MPMol Pharm 2018 Jul 18
- The formulation of oral amorphous solid dispersions (ASD) includes the use of excipients to improve physical stability and enhance bioavailability. Combinations of excipients (polymers and surfactant...
The formulation of oral amorphous solid dispersions (ASD) includes the use of excipients to improve physical stability and enhance bioavailability. Combinations of excipients (polymers and surfactants) are often employed in pharmaceutical products to improve the delivery of poorly water-soluble drugs. However, additive interactions in multi-component ASD systems have not been extensively studied and may promote crystallization in an unpredictable manner, which in turn may affect the physical stability and dissolution profile of the product. The main aim of this study was to understand the effect of different surfactant and polymer combinations on the solid-state properties and dissolution behaviour of ternary spray dried solid dispersions of dipyridamole and cinnarizine. The surfactants chosen for this study were sodium dodecyl sulphate and poloxamer 188 and the model polymers used are polyvinyl pyrrolidone K30 and hydroxypropyl methylcellulose K100. The spray dried ternary dispersions maintained higher supersaturation compared to either the crystalline drug equilibrium solubility or their respective physical mixtures. However, rapid and variable dissolution behaviour was observed for different formulations. The maximum supersaturation level was observed with drug-polymer-polymer ternary dispersions. On the other hand, incorporating the surfactant into binary (drug-polymer) and ternary (drug-polymer-polymer) ASDs adversely affected the physical stability and dissolution by promoting crystallization. Based on these observations, a thorough investigation into the impact of combinations of additives on amorphous drug crystallization during dissolution and stability studies is recommended in order to develop optimized formulations of supersaturating dosage forms.
- Combination therapy with or without warfarin and dipyridamole for severe childhood IgA nephropathy: an RCT. [Journal Article]
- PNPediatr Nephrol 2018 Jul 09
- CONCLUSIONS: The balance between minimal benefits of warfarin/dipyridamole and potential adverse effects may be in favor of avoiding them in children with IgA nephropathy.
- Non-contrast assessment of microvascular integrity using arterial spin labeled cardiovascular magnetic resonance in a porcine model of acute myocardial infarction. [Journal Article]
- JCJ Cardiovasc Magn Reson 2018 Jul 02; 20(1):45
- CONCLUSIONS: ASL-CMR can assess vasodilator response in healthy swine and detect significant reduction in regional MBF at rest following AMI. ASL-CMR is an alternative to gadolinium-based techniques for assessment of MVO and microvascular integrity within infarcted, as well as salvageable and remote myocardium. This has the potential to provide early indications of adverse remodeling processes post-ischemia.
- Better characterization of dipyridamole-induced myocardial stunning by systolic wall thickening. A gated perfusion SPECT study. [Journal Article]
- JNJ Nucl Cardiol 2018 Jun 27
- CONCLUSIONS: WT-SDS showed a better correlation with the degree of ischemia than the depression in the global function of the left ventricle. It allowed to better identify the stunning phenomenon in patients submitted to pharmacological stress.
- Prescribing patterns of oral antiplatelets in Wales: evolving trends from 2005 to 2016. [Journal Article]
- FCFuture Cardiol 2018 Jun 25
- CONCLUSIONS: This first-look analysis of real-life antiplatelet data demonstrates a decrease in the overall prescribing costs with varying patterns. This may aid policy-makers in reviewing funding strategies.
- Influence of Polymers on the Physical and Chemical Stability of Spray-dried Amorphous Solid Dispersion: Dipyridamole Degradation Induced by Enteric Polymers. [Journal Article]
- APAAPS PharmSciTech 2018 Jun 18
- Amorphous solid dispersions (ASDs) are inherently unstable because of high internal energy. Evaluating physical and chemical stability during the process and storage is essential. Numerous researches...
Amorphous solid dispersions (ASDs) are inherently unstable because of high internal energy. Evaluating physical and chemical stability during the process and storage is essential. Numerous researches have demonstrated how polymers influence the drug precipitation and physical stability of ASDs, while the influence of polymers on the chemical stability of ASDs is often overlooked. Therefore, this study aimed to investigate the effect of polymers on the physical and chemical stability of spray-dried ASDs using dipyridamole (DP) as a model drug. Proper polymers were selected by assessing their abilities to inhibit drug recrystallization in supersaturated solutions. HPMC E5, Soluplus®, HPMCP-55, and HPMCAS-LP were shown to be effective stabilizers. The optimized formulations were further stored at a high temperature (60 °C) and high humidity (40 °C, 75% RH) for 2 months, and their physical and chemical stability was evaluated using polarizing optical microscopy, FTIR, HPLC, and mass spectrometry (MS). In general, crystallization was observed in all samples, which indicated the physical instability under stressed storage conditions. Also, it was noted that the polymers in ASDs rather than physical mixtures, induced a dramatic drug degradation after being exposed to a high temperature (HPMCP-55 > 80% and HPMCAS-LP > 50%) and high humidity (HPMCP-55 > 40% and HPMCAS-LP > 10%). The MS analysis further confirmed the degradation products, which might be generated from the reaction between dipyridamole and phthalic anhydride decomposed from HPMCP-55 and HPMCAS-LP. Overall, the exposure of ASDs to stressed conditions resulted in recrystallization and even the chemical degradation induced by polymers.
- Capillary leak syndrome and aseptic meningitis in a patient with Kawasaki disease: A case report. [Case Reports]
- MMedicine (Baltimore) 2018; 97(23):e10716
- CONCLUSIONS: The incidence of KD has recently increased and cardiovascular complications are frequently reported. This may be combined with systemic damage, however, the combination of SCLS and aseptic meningitis is rarely reported, therefor, children who have SCLS, aseptic meningitis and unexplained fever >5 days, KD should be taken into account. Early diagnosis and timely treatment can reduce complications induced by KD.
- Long-Term Association of Dipyridamole Stress Myocardial Contrast Echocardiography versus Single-Photon Emission Computed Tomography with Clinical Outcomes in Patients with Known or Suspected Coronary Artery Disease. [Journal Article]
- JAJ Am Soc Echocardiogr 2018 May 31
- CONCLUSIONS: MCE but not SPECT showed a long-term association with outcome. These results thus favor the routine use of MCE in the long-term assessment of patients with known or suspected coronary artery disease.
- Tunable Elastomers with an Antithrombotic Component for Cardiovascular Applications. [Journal Article]
- AHAdv Healthc Mater 2018 May 31; :e1800222
- This study reports the development of a novel family of biodegradable polyurethanes for use as tissue engineered cardiovascular scaffolds or blood-contacting medical devices. Covalent incorporation o...
This study reports the development of a novel family of biodegradable polyurethanes for use as tissue engineered cardiovascular scaffolds or blood-contacting medical devices. Covalent incorporation of the antiplatelet agent dipyridamole into biodegradable polycaprolactone-based polyurethanes yields biocompatible materials with improved thromboresistance and tunable mechanical strength and elasticity. Altering the ratio of the dipyridamole to the diisocyanate linking unit and the polycaprolactone macromer enables control over both the drug content and the polymer cross-link density. Covalent cross-linking in the materials achieves significant elasticity and a tunable range of elastic moduli similar to that of native cardiovascular tissues. Interestingly, the cross-link density of the polyurethanes is inversely related to the elastic modulus, an effect attributed to decreasing crystallinity in the more cross-linked polymers. In vitro characterization shows that the antiplatelet agent is homogeneously distributed in the materials and is released slowly throughout the polymer degradation process. The drug-containing polyurethanes support endothelial cell and vascular smooth muscle cell proliferation, while demonstrating reduced levels of platelet adhesion and activation, supporting their candidacy as promising substrates for cardiovascular tissue engineering.
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- Application of an in vitro dissolution/permeation system to early screening of oral formulations of poorly soluble, weakly basic drugs containing an acidic pH-modifier. [Journal Article]
- JPJ Pharm Sci 2018 May 23
- This study aimed to evaluate the usefulness of the dissolution/permeation system (D/P system) as an in vitro tool for early screening of oral formulations of weak basic drugs containing an acidic pH ...
This study aimed to evaluate the usefulness of the dissolution/permeation system (D/P system) as an in vitro tool for early screening of oral formulations of weak basic drugs containing an acidic pH modifier. Dipyridamole, having a prominent pH-dependent solubility, was used as a model drug and various granules containing different amounts of fumaric acid were prepared. Prepared granules were administered orally to hypochlorhydria model rats. It was confirmed that fumaric acid improved the absorption of dipyridamole depending on its amount in the granules. Separately, dissolution and permeation of dipyridamole were observed in vitro in the D/P system. When using a medium with a low buffer capacity which mimicked the human intestinal fluid, rank order of the permeated amount of dipyridamole from various granules in the D/P system did not correlate with its absorption in hypochlorhydric rats. In contrast, when applying a medium with high buffer capacity, the permeated amount in the D/P system well reflected the effects of fumaric acid on the in vivo absorption of dipyridamole. In conclusion, by setting appropriate experimental protocols according to the properties of test compounds and formulations, D/P system can be a potent in vitro tool to predict in vivo performance of oral formulations.