Amorphous Drug-PVP Dispersions: Application of Theoretical, Thermal and Spectroscopic Analytical Techniques to the Study of a Molecule With Intermolecular Bonds in Both the Crystalline and Pure Amorphous State

Tobyn, Mike; Brown, Jonathan; Dennis, Andrew B.; Fakes, Michael G.; Gao, Qi; Gamble, John F.; Khimyak, Yaroslav Z.; McGeorge, Gary; Patel, Chhaya; Sinclair, Wayne E.; Timmins, Peter; Yin, Shawn

doi:10.1002/jps.21738

Cited by 85 publications

(72 citation statements)

References 24 publications

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“…Tobyn et al 35) used these equations to determine the T g of an amorphous drug-PVP binary system. In this study, the predicted T g in PC fiber was approximately 164.14°C.…”

Section: )mentioning

confidence: 99%

Intermolecular Interactions and the Release Pattern of Electrospun Curcumin-Polyvinyl(pyrrolidone) Fiber

Rahma

Munir

Khairurrijal

et al. 2016

Biological & Pharmaceutical Bulletin

167

104

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An electrospun fiber of polyvinyl(pyrrolidone) (PVP)-Tween 20 (T20) with curcumin as the encapsulated drug has been developed. A study of intermolecular interactions was performed using Raman spectroscopy, Fourier transform infrared (FT-IR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD).The Raman and FT-IR studies showed that curcumin preferrably interacted with T20 and altered PVP chain packing, as supported by XRD and physical stability data. The hydroxyl stretching band in PVP shifted to a lower wavenumber with higher intenstity in the presence of curcumin and PVP, indicating that hydrogen bond formation is more intense in a curcumin or curcumin-T20 containing fiber. The thermal pattern of the fiber did not indicate phase separation. The conversion of curcumin into an amorphous state was confirmed by XRD analysis. An in vitro release study in phosphate buffer pH 6.8 showed that intermolecular interactions between each material influenced the drug release rate. However, low porosity was found to limit the hydrogen bond-mediated release.Key words curcumin; fiber; electrospinning; interaction; porosity; polymeric drug delivery system Curcumin is the major constituent of turmeric rhizome (Curcuma sp.).1) Curcumin has a number of demonstrated pharmacological effects, such as antioxidant, anti-inflammatory, anticancer, hepatoprotective, 1) antimicrobial, and antiviral. 2)Clinical trials have proven that curcumin is well tolerated by the body, with a maximum dose of 12 g daily.3) Unfortunately, the efficacy of curcumin is limited by its poor solubility in water, as well as its instability under light, heat, and alkaline conditions.1) The solubility of curcumin in aqueous buffer (pH 5) is reported to be 11 ng/mL.3) Moreover, the absorption of curcumin in the gastrointestinal tract is very low, leading to poor bioavailability (in animals and humans).2) Therefore, designing an effective delivery system is necessary in order to address the limitations of curcumin use. 1-3)A wide range of drug delivery systems has been developed to improve the bioavailability of poorly soluble drugs, including fast-dissolving tablets, 4) incorporation into a hydrophilic complex, 1) micellization, and solid dispersion. 5) Electrospinning, a technique of producing thin strands of fiber using high voltage, has opened up opportunities in the development of drug delivery systems. An optimized electrospinning process can produce nano-sized fibers. 6)The high surface area and porosity of these electrospun fibers are advantageous in their use as carriers for poorly water-soluble drugs.5) The high surface area generally increases the dissolution rate of the incorporated drug, thus potentially enhancing its bioavailability. 5)Therefore, the incorporation of curcumin into an electrospun fiber is expected to improve its oral bioavailability.Tailoring a suitable drug-loaded fiber requires careful selection of materials, in addition to an optimized production process and environment. Generally, the drug is mixed with a polymer s...

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“…Tobyn et al 35) used these equations to determine the T g of an amorphous drug-PVP binary system. In this study, the predicted T g in PC fiber was approximately 164.14°C.…”

Section: )mentioning

confidence: 99%

Intermolecular Interactions and the Release Pattern of Electrospun Curcumin-Polyvinyl(pyrrolidone) Fiber

Rahma

Munir

Khairurrijal

et al. 2016

Biological & Pharmaceutical Bulletin

167

104

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“…The physicochemical properties of the amorphous materials vary in the glassy compared to the supercooled state [7]. Amorphous solids in the glassy state have rheological properties of solids, but have a high molecular mobility [8].…”

Section: Introductionmentioning

confidence: 99%

Pharmaceutical solvates, hydrates and amorphous forms: A special emphasis on cocrystals

Healy

Worku

Kumar

et al. 2017

Advanced Drug Delivery Reviews

282

189

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a b s t r a c t a r t i c l e i n f oActive pharmaceutical ingredients (APIs) may exist in various solid forms, which can lead to differences in the intermolecular interactions, affecting the internal energy and enthalpy, and the degree of disorder, affecting the entropy. Differences in solid forms often lead to differences in thermodynamic parameters and physicochemical properties for example solubility, dissolution rate, stability and mechanical properties of APIs and excipients. Hence, solid forms of APIs play a vital role in drug discovery and development in the context of optimization of bioavailability, filing intellectual property rights and developing suitable manufacturing methods. In this review, the fundamental characteristics and trends observed for pharmaceutical hydrates, solvates and amorphous forms are presented, with special emphasis, due to their relative abundance, on pharmaceutical hydrates with single and two-component (i.e. cocrystal) host molecules.

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“…Amorphous substances show altered physico-chemical properties in comparison to their crystalline counterparts (9). Consequently, they often exhibit improved solubility, enhanced dissolution rate, and improved bioavailability (11)(12)(13)(14)(15)(16). Amorphization can be achieved by various routes, i.e., (i) solvent evaporation, (ii) milling, (iii) freeze-or spray drying, and (iv) quench cooling.…”

Section: Introductionmentioning

confidence: 99%

“…However, amorphous substances are often labile and therefore stability issues frequently become the major challenge of the formulation efforts. One of the opportunities to stabilize amorphous APIs is the addition of excipients to suppress recrystallization: Examples of materials to suppress recrystallization are polymers and low molecular weight compounds, such as amino acids, polyhydroxy alcohols, traditional as well as modified saccharides Recently, the importance of acetylated derivatives of saccharides has been emphasized (14)(15)(16). These substances are cost-effective and are widely used in the food industry.…”

Section: Introductionmentioning

confidence: 99%

“…Commercially available formulations, e.g., polymer matrix systems with erosion-driven drug release or oral osmotic systems (OROS) with osmotically controlled drug delivery, involve various mechanisms to obtain appropriate drug dissolution. Besides indisputable advantages of such formulations, there are also some drawbacks with regards to high costs and complexity of the systems, limited usefulness for application with poorly soluble APIs, or risk of toxicity increase due to dose dumping (e.g., in the case of coating perforation (15,19,20)). For these reasons, there is still need to contemplate novel strategies for controlled delivery of poorly soluble drugs.…”

Section: Introductionmentioning

confidence: 99%

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Melts of Octaacetyl Sucrose as Oral-Modified Release Dosage Forms for Delivery of Poorly Soluble Compound in Stable Amorphous Form

Haznar-Garbacz

Kamińska

Żakowiecki³

et al. 2017

AAPS PharmSciTech

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Abstract. The presented work describes the formulation and characterization of modified release glassy solid dosage forms (GSDFs) containing an amorphous nifedipine, as a model BCS (Biopharmaceutical Classification System) class II drug. The GSDFs were prepared by melting nifedipine together with octaacetyl sucrose. Dissolution profiles, measured under standard and biorelevant conditions, were compared to those obtained from commercially available formulations containing nifedipine such as modified release (MR) tablets and osmotic release oral system (OROS). The results indicate that the dissolution profiles of the GSDFs with nifedipine are neither affected by the pH of the dissolution media, type and concentration of surfactants, nor by simulated mechanical stress of biorelevant intensity. Furthermore, it was found that the dissolution profiles of the novel dosage forms were similar to the profiles obtained from the nifedipine OROS. The formulation of GSDFs is relatively simple, and the dosage forms were found to have favorable dissolution characteristics.

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Amorphous Drug-PVP Dispersions: Application of Theoretical, Thermal and Spectroscopic Analytical Techniques to the Study of a Molecule With Intermolecular Bonds in Both the Crystalline and Pure Amorphous State

Cited by 85 publications

References 24 publications

Intermolecular Interactions and the Release Pattern of Electrospun Curcumin-Polyvinyl(pyrrolidone) Fiber

Intermolecular Interactions and the Release Pattern of Electrospun Curcumin-Polyvinyl(pyrrolidone) Fiber

Pharmaceutical solvates, hydrates and amorphous forms: A special emphasis on cocrystals

Melts of Octaacetyl Sucrose as Oral-Modified Release Dosage Forms for Delivery of Poorly Soluble Compound in Stable Amorphous Form

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