The Effect of Glucose and Poloxamer 188 on Red-Blood-Cell Aggregation

Glucose metabolism disorders contribute to the development of various diseases. Numerous studies show that these disorders not only change the normal values of biochemical parameters but also affect the mechanical properties of blood. To show the influence of glucose and poloxamer 188 (P188) on the mechanical properties of a red-blood-cell (RBC) suspension, we studied the aggregation of the cells. To show the mechanisms of the mechanical properties of blood, we studied the effects of glucose and poloxamer 188 (P188) on red-blood-cell aggregation. We used a model in which cells were suspended in a dextran 70 solution at a concentration of 2 g/dL with glucose and P188 at concentrations of 0–3 g/dL and 0–3 mg/mL, respectively. RBC aggregation was determined using an aggregometer, and measurements were performed every 4 min for 1 h. Such a procedure enabled the incubation of RBCs in solution. The aggregation index determined from the obtained syllectograms was used as a measure of aggregation. Both the presence of glucose and that of P188 increased the aggregation index with the incubation time until saturation was reached. The time needed for the saturation of the aggregation index increased with increasing glucose and P188 concentrations. As the concentrations of these components increased, the joint effect of glucose and P188 increased the weakening of RBC aggregation. The mechanisms of the observed changes in RBC aggregation in glucose and P188 solutions are discussed.

Improving Tableting Performance of Lactose Monohydrate by Fluid-Bed Melt Granulation Co-Processing

Co-processing is commonly used approach to improve functional characteristics of pharmaceutical excipients to become suitable for tablet production by direct compression. This study aimed to improve tableting characteristics of lactose monohydrate (LMH) by co-processing by fluid-bed melt granulation with addition of hydrophilic (PEG 4000 and poloxamer 188) and lipophilic (glyceryl palmitostearate) meltable binders. In addition to binding purpose, hydrophilic and lipophilic excipients were added to achieve self-lubricating properties of mixture. Co-processed mixtures exhibit superior flow properties compared to pure LMH and comparable or better flowability relative to commercial excipient Ludipress®. Compaction of mixtures co-processed with 20% PEG 4000 and 20% poloxamer 188 resulted in tablets with acceptable tensile strength (>2 MPa) and good lubricating properties (ejection and detachment stress values below 5 MPa) in a wide range of compression pressures. While the best lubricating properties were observed when glyceryl palmitostearate was used as meltable binder, obtained tablets failed to fulfil required mechanical characteristics. Although addition of meltable binder improves interparticle bonding, disintegration time was not prolonged compared to commercial excipient Ludipress®. Co-processed mixtures containing 20% of either PEG 4000 or poloxamer 188 showed superior tabletability and lubricant properties relative to LMH and Ludipress® and can be good candidates for tablet production by direct compression.

The Promising Role of Chitosan–Poloxamer 188 Nanocrystals in Improving Diosmin Dissolution and Therapeutic Efficacy against Ferrous Sulfate-Induced Hepatic Injury in Rats

Diosmin (DSN) exhibits poor water solubility and low bioavailability. Although nanocrystals (NCs) are successful for improving drug solubility, they may undergo crystal growth. Therefore, DSN NCs were prepared, employing sonoprecipitation utilizing different stabilizers. The optimum stabilizer was combined with chitosan (CS) as an electrostatic stabilizer. NCs based on 0.15% w/v poloxamer 188 (PLX188) as a steric stabilizer and 0.04% w/v CS were selected because they showed the smallest diameter (368.93 ± 0.47 nm) and the highest ζ-potential (+40.43 ± 0.15 mV). Mannitol (1% w/v) hindered NC enlargement on lyophilization. FT-IR negated the chemical interaction of NC components. DSC and XRD were performed to verify the crystalline state. DSN dissolution enhancement was attributed to the nanometric rod-shaped NCs, the high surface area, and the improved wettability. CS insolubility and its diffusion layer may explain controlled DSN release from CS-PLX188 NCs. CS-PLX188 NCs were more stable than PLX188 NCs, suggesting the significance of the combined electrostatic and steric stabilization strategies. The superiority of CS-PLX188 NCs was indicated by the significantly regulated biomarkers, pathological alterations, and inducible nitric oxide synthase (iNOS) expression of the hepatic tissue compared to DSN suspension and PLX188 NCs. Permeation, mucoadhesion, and cellular uptake enhancement by CS may explain this superiority.

Formulation of Genistein-HP β Cyclodextrin-Poloxamer 188 Ternary Inclusion Complex: Solubility to Cytotoxicity Assessment

The current study was designed to prepare the inclusion complex Genistein (GS) using Hydroxypropyl β cyclodextrin (HP β CD) and poloxamer 188 (PL 188). The binary inclusion complex (GS BC) and ternary inclusion complex (GS TC) were developed by microwave irradiation technique and evaluated for a comparative dissolution study. Further, the samples were assessed for FTIR, DSC, XRD, and NMR for the confirmation of complex formation. Finally, antioxidant and antimicrobial studies and cytotoxicity studies on a breast cancer (MCF-7) cell line were conducted. The dissolution study result showed a marked increment in GS dissolution/release after incorporation in binary (GS: HP β CD, 1:1) and ternary (GS: HP β CD: PL 188; 1:1:0.5) inclusion complexes. Moreover, the ternary complex exhibited a significant enhancement (p < 0.05) in dissolution than did the binary complexes. This might be due to the presence of PL 188, which helps in solubility enhancement of GS. DSC, XRD and SEM evaluation confirmed the modification in the structure of GS. FTIR and NMR results indicated the formation of an inclusion complex. The antioxidant and antimicrobial activity results revealed that GS TC has shown significant (p < 0.05) higher activity than pure GS. The cytotoxicity study results also depicted concentration-dependent cytotoxicity. GS TC exhibited significantly (p < 0.05) high cytotoxicity to cancer cells (IC50 = 225 µg/mL) than pure GS (IC50 = 480 µg/mL). Finally, it was concluded that a remarkable enhancement in the dissolution was observed after the inclusion of GS in the ternary complex and it therefore has significant potential for the treatment of breast cancer.

In Vitro and In Vivo Evaluation of Oral Controlled Release Formulation of BCS Class I Drug Using Polymer Matrix System

Diltiazem hydrochloride is a calcium channel blocker, which belongs to the family of benzothiazepines. It is commonly used to treat hypertension and atrial fibrillation. Even though the drug has high solubility, its high permeability and rapid metabolism in the liver can limit the bioavailability and increase the dose frequencies for up to four times per day. This study focused on a polymer matrix system not only to control the drug release but also to prolong the duration of bioavailability. The polymer matrices were prepared using different ratios of poloxamer-188, hydroxypropyl methylcellulose, and stearyl alcohol. In vitro and in vivo assessments took place using 24 rabbits and the results were compared to commercially available product Tildiem® (60 mg tablet) as reference. Overall, the rate of drug release was sustained with the gradual increase of poloxamer-188 incorporated with hydroxypropyl methylcellulose and stearyl alcohol in the matrix system, achieving a maximum release period of 10 h. The oral bioavailability and pharmacokinetic parameters of diltiazem hydrochloride incorporated in polymer matrix system were similar to commercial reference Tildiem®. In conclusion, the combination of polymers can have a substantial effect on controlling and prolonging the drug release pattern. The outcomes showed that poloxamer-188 combined with hydroxypropyl methylcellulose and stearyl alcohol is a powerful matrix system for controlling release of diltiazem hydrochloride.