Improvement Of Physical Stability Research Articles

In Situ Cocrystallization via Spray Drying with Polymer as a Strategy to Prevent Cocrystal Dissociation.

The aim of the present study was to investigate how different polymers affect the dissociation of cocrystals prepared by co-spray-drying active pharmaceutical ingredient (API), coformer, and polymer. Diclofenac acid-l-proline cocrystal (DPCC) was selected in this study as a model cocrystal due to its previously reported poor physical stability in a high-humidity environment. Polymers investigated include polyvinylpyrrolidone (PVP), poly(1-vinylpyrrolidone-co-vinyl acetate) (PVPVA), hydroxypropyl methyl cellulose, hydroxypropylmethylcellulose acetate succinate, ethyl cellulose, and Eudragit L-100. Terahertz Raman spectroscopy (THz Raman) and powder X-ray diffraction (PXRD) were used to monitor the cocrystal dissociation rate in a high-humidity environment. A Raman probe was used in situ to monitor the extent of the dissociation of DPCC and DPCC in crystalline solid dispersions (CSDs) with polymer when exposed to pH 6.8 phosphate buffer and water. The solubility of DPCC and solid dispersions of DPCC in pH 6.8 phosphate buffer and water was also measured. The dissociation of DPCC was water-mediated, and more than 60% of DPCC dissociated in 18 h at 40 °C and 95% RH. Interestingly, the physical stability of the cocrystal was effectively improved by producing CSDs with polymers. The inclusion of just 1 wt % polymer in a CSD with DPCC protected the cocrystal from dissociation over 18 h under the same conditions. Furthermore, the CSD with PVPVA was still partially stable, and the CSD with PVP was stable (undissociated) after 7 days. The superior stability of DPCC in CSDs with PVP and PVPVA was also demonstrated when systems were exposed to water or pH 6.8 phosphate buffer and resulted in higher dynamic solubility of the CSDs compared to DPCC alone. The improvement in physical stability of the cocrystal in CSDs was thought to be due to an efficient mixing between polymer and cocrystal at the molecular level provided by spray drying and in situ gelling of polymer. It is hypothesized that polymer chains could undergo gelling in situ and form a physical barrier, preventing cocrystal interaction with water, which contributes to slowing down the water-mediated dissociation.

Study on model plant based functional beverage emulsion (non-dairy) using ultrasound – A physicochemical and functional characterization

This study reports the development of non-dairy functional beverage emulsion employing ultrasound (US) of 20 kHz at 130 W and 195 W at processing times of 2 to 8 min using chickpea milk extract and bioactive, flaxseed oil (4%). The pre-emulsion was formed with high shear homogenizer followed by main sonication process. The sonicated emulsions were stored at 4 ± 2 °C till 14 days and characterized for physicochemical and functional properties. A comparative study was carried out using conventional high shear homogenizer (UT) at 10,000 RPM for 5 min. Upon optimization, 130 W − 8 min, 195 W − 6 min and 195 W – 8 min sono-emulsions showed creaming stability of 100%; with particle sizes as 1.12, 0.97 and 0.78 µm; and zetapotential values as − 40.4 mV, −37.52 and −36.91 mV, respectively. The improvement in protein solubility by 86% proved the emulsifying capability of chickpea proteins, which had partially denatured upon physical effects of acoustic cavitation producing stable and finer emulsion droplets. The reduced sedimentation values of sonicated chickpea extract in comparison to UT showed improvement in physical stability of plant-based milk. Oxidative stability is observed for 130 W − 8 min sonicated emulsions with no change in conjugated dienes, indicating the absence of process generated free radicals. The US process did not have any effect on reduction of stachyose content. But extracted chickpea milk had lower amount of stachyose in comparison to raw chickpeas, reducing the flatulence problem, mainly due to adaptation of high temperature pressure cooking process.

Influence of a shear post-treatment on rheological properties, microstructure and physical stability of emulgels formed by rosemary essential oil and a fumed silica

Nanoemulsions containing rosemary essential oil, a natural food preservative, were developed by the microfluidization technique and emulgels were formed by adding a fumed silica (Aerosil 200). The influence of homogenization pressure on droplet size was examined. The nanoemulsion prepared at 5000 psi in Microfluidizer showed the lowest Sauter diameter and it was selected as the starting point. The influence of shear on rheological properties, stability and microstructure was studied for both the nanoemulsion and the emulgel formed. The emulsion showed recoalescence induced by shear, while the emulgel exhibited an alignment of a 3D-network. In addition, the prepared emulgel exhibited time-dependent behaviour. In spite of the fact that the viscoelastic functions of the emulgel decreased as a result of shear, a significant improvement in physical stability was detected by means of the Multiple Light Scattering technique.

The influence of flaxseed gum on the microrheological properties and physicochemical stability of whey protein stabilized β-carotene emulsions.

The impact of flaxseed gum (FG) on the microrheological properties and physicochemical stability of whey protein isolate (WPI) stabilized β-carotene emulsions at pH 3.0 was studied. A layer-by-layer electrostatic deposition method was used to prepare multilayered β-carotene emulsions with interfacial membranes consisting of WPI and FG. The microrheological behavior of the multilayered β-carotene emulsions was measured through the diffusive wave spectroscopy technique. WPI alone and WPI-FG (concentration of FG = 0.1, 0.2, 0.3 wt%) stabilized β-carotene emulsions were purely viscous giving a mean square displacement that scaled linearly with decorrelation time (τ). The presence of 0.01, 0.02, and 0.05 wt% FG in the WPI-stabilized emulsions caused them to exhibit viscoelastic properties. Meanwhile, the increase in τ reflected the increase in the length scale of connectivity in the emulsions until a "cluster" was formed and the droplets were not free to move due to droplet-network interaction. The apparent increase in the macroscopic viscosity and elasticity index and decrease in the solid lipid balance and fluidity index of emulsions with lower concentrations (0.01, 0.02, 0.05 wt%) of FG indicated that the bridging flocculation of FG had a much more appreciable influence on the microrheological properties than depletion flocculation (higher concentrations, 0.1, 0.2, 0.3 wt%). Droplet size, zeta-potential, and transmission profiles using the centrifugal sedimentation technique and β-carotene degradation during storage were also characterized. With the addition of FG, the zeta-potential of WPI coated β-carotene droplets decreased from positive to negative, and an increase in the apparent droplet size was also noted. LUMISizer analysis exhibited an improvement in physical stability with the addition of 0.1 wt% FG. FG also helped to chemically stabilize the WPI emulsions against β-carotene degradation mainly by slowing down the mobility of the droplets.

Length-scale Specific Crystalline Structural Changes Induced by Molecular Randomization of Pequi Oil.

Pequi fruit (Caryocar brasiliense Camb) is considered important since its pulp has a high content of oil and carotenoids. The oil's triacylglycerols (TAGs) contain mainly oleic (~57%) and palmitic (~36%) fatty acids, distributed primarily among POO, POP/PPO, and OOO TAGs. It displays a tendency to fractionate upon storage and has a relatively low melting temperature (SFC of 4% at 25°C). Pequi oil was modified through chemical interesterification, which increased the PPP content to ~6%. This caused a flattening in the SFC-temperature profile, raising the end of melt temperature significantly (SFC of 4% at 39°C). The interesterified oil does not fractionate and is thermally stable up to 40°C, with an SFC-temperature profile resembling that of roll-in shortening (SFC of 31% at 16°C) despite containing high amounts of oleic acid. Crystallization and melting behavior changed. Crystal packing became more disorganized as evidenced by a significant decrease in crystalline domain size in the [001] direction from 42.3 nm to 32.1 nm. Polymorphism remained of the triclinic (β) subcell type but polytypism changed from the 3L to the 2L type. Polarized light microscopy demonstrated that interesterification dramatically decreased crystal size, consistent with a higher rate of nucleation in the material. Moreover, the dramatic improvement in physical stability and functionality was not accompanied by a significant decrease in total carotenoid content (~390 mg/kg).

Modified NLC-loaded coumarin for pharmaceutical applications: the improvement of physical stability and controlled release profile

Background: Coumarin-6 is a lipophilic dye and is often used as a model in delivery system.Objective: The aim of this study was to improve the nonstructured lipid carrier (NLC) system loading with lipophilic molecule, coumarin-6, and to investigate its characteristics in terms of physical stability and controlled release profile.Materials and methods: Initially, the selection of the coating polymer was observed. Then, the preparation of the conventional NLC-loaded coumarin-6 was compared to the modified NLC-loaded coumarin-6 via the probe sonication. The physical properties and stability were determined by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and X-ray diffraction (XRD) techniques. The release profile was established using fluorescent spectroscopic method.Results and discussion: The size and zeta potential measurement showed significant decrease in the size range of the modified NLC-loaded coumarin and the lower intensity of the surface charge compared to the NLC-loaded coumarin. The change of crystallinity observed from DSC and XRD techniques indicated the molecular dispersion of coumarin-6 in the lipid matrix of NLC. The FT-IR spectra were also proven that coumarin-6 was entrapped in the NLC molecule. The result showed comparable controlled release profile to the conventional preparation with no difference on the cytotoxicity level.Conclusions: The modified NLC delivery system, therefore, exhibited the acceptable potential as a nanocarrier.

Impact of chitosan–EGCG conjugates on physicochemical stability of β-carotene emulsion

The aim of the present study was to investigate the effects of low-molecular-weight chitosan (LC)–(−)-epigallocatechin-3-gallate (EGCG) conjugates on the physicochemical properties of oil-in-water emulsions incorporating β-carotene within the oil droplets. Covalent coupling of LC to EGCG was achieved by hydroxyl-free radical grafting. The physicochemical stability of β-carotene emulsions was characterized by droplet size and distribution, rheological behavior, transmission profiles using novel centrifugal sedimentation and β-carotene degradation in the emulsion during storage. β-Carotene emulsions stabilized by LC–EGCG conjugates had relatively smaller mean droplet size, more homogenous droplet size distribution and less change in centrifugal transmission profiles, indicating a substantial improvement in physical stability. Degradation of β-carotene in emulsions during storage was significantly retarded by LC–EGCG conjugates than native LC (formed without the redox pair and without EGCG) and control LC (formed with redox pair and without EGCG). These results implied that LC–EGCG conjugates were able to improve the physical stability of β-carotene emulsion and inhibit the deterioration of β-carotene in oil-in-water emulsions.

Physical stability enhancement of theophylline via cocrystallization

The crystal form adopted by the respiratory drug theophylline was modified using a crystal engineering strategy in order to search for a solid material with improved physical stability. Cocrystals, also referred to as crystalline molecular complexes, were prepared with theophylline and one of several dicarboxylic acids. Four cocrystals of theophylline are reported, one each with oxalic, malonic, maleic and glutaric acids. Crystal structures were obtained for each cocrystal material, allowing an examination of the hydrogen bonding and crystal packing features. The cocrystal design scheme was partly based upon a series of recently reported cocrystals of the molecular analogue, caffeine, and comparisons in packing features are drawn between the two cocrystal series. The theophylline cocrystals were subjected to relative humidity challenges in order to assess their stability in relation to crystalline theophylline anhydrate and the equivalent caffeine cocrystals. None of the cocrystals in this study converted into a hydrated cocrystal upon storage at high relative humidity. Furthermore, the theophylline:oxalic acid cocrystal demonstrated superior humidity stability to theophylline anhydrate under the conditions examined, while the other cocrystals appeared to offer comparable stability to that of theophylline anhydrate. The results demonstrate the feasibility of pharmaceutical cocrystal design based upon the crystallization preferences of a molecular analogue, and furthermore show that avoidance of hydrate formation and improvement in physical stability is possible via pharmaceutical cocrystallization.

Preparation and properties of poly(vinyl alcohol)-stabilized liposomes

The purpose of this work is to evaluate the improvement in physical stability of poly(vinyl alcohol) (PVA) modified liposomes. Liposomes composed of soya phosphatidylcholile (SPC) and cholesterol (1:1 molar ratio) were prepared by reverse phase evaporation method. Two types of interaction between liposome and PVA were investigated: PVA addition into lipid bilayer during liposome preparation and coating of already formed liposomes with PVA. The microparticles system was morphologically characterized by transmission electron microscopy (TEM) and particles analysis. Changes in particles size and zeta potential confirmed the existence of a thick polymer layer on the surface of liposomes. The amount of PVA adsorbing to liposomes and the encapsulation efficiency increased with increasing polymer concentration. The physical stability was evaluated by measuring the release rate of contents at 20 and 37 °C, the PVA modified liposomes were more stable than the conventional liposomes. Comparing with PVA-coated liposomes, the liposomes with PVA addition to the bilayer were more stable, and had higher entrapment efficiency.

Physical stability of size controlled small unilameller liposomes coated with a modified polyvinyl alcohol

The purpose of this work is to evaluate the improvement in physical stability of polymer coated liposomes. Small unilamellar liposomes (dimilistoylphosphatidylcholine (DMPC): dicetyl phosphate (DCP): cholesterol (Chol)=7:3:1) 100 nm in diameter were coated with polyvinyl alcohol (PVA) and a modified PVA, which bears a long alkyl chain at the end of molecule (PVA-R), by simply mixing the liposomal suspension with the polymer solutions. Changes in particle size and zeta potential for the polymer coated liposomes confirmed the existence of a thick polymer layer on the surface of liposomes, especially for the PVA-R coated liposomes. The amount of PVA-R coating increased with increasing polymer concentration, and the estimated molar ratio of PVA-R coating to phospholipids in the liposomes was 1/120 at the highest polymer concentration (2%). The physical stability of polymer coated liposomes was evaluated by measuring the change in particle size and the retention of entrapped contents after perturbing the system with freeze-drying and followed by rehydration (FD-RH). PVA-R coated liposomes showed almost complete retention of particle size and a larger entrapped content, while a dramatic increase in particle size and a reduction in the percentage entrapped, which suggested the occurrence of aggregation and fusion of liposome particles during FD-RH, were observed for non-coated and PVA-coated liposomes. Aggregation of liposomes in calf serum was effectively prevented by coating liposomes with PVA-R.