Search Results (5)

Poor drug entrapment, burst release, and variable drug release profiles are the most critical challenges associated with biodegradable-polymer-based microspheres. In this study, biodegradable-polymer-based microspheres were used to entrap an antiplatelet drug, eptifibatide, using a single-emulsion solvent evaporation method. Critical challenges associated with biodegradable-polymer-based microspheres were addressed by incorporating different additives in the drug or polymer phase. Additives such as hydroxy propyl beta cyclodextrins (HPβCD), carboxy methyl cellulose sodium (Na CMC), and trehalose were added to the drug phase to evaluate their impact on the entrapment and stability of eptifibatide. The effect of the addition of additives such as polyvinyl alcohol (PVA), polyethylene glycol-400 (PEG-400), and methoxy polyethylene glycol phospholipid dimyristoyl phosphatidylethanolamine (mPEG-2000-DMPE, Na) to the polymer phase on the release profile of eptifibatide was evaluated. The inclusion of HPβCD resulted in good drug entrapment and helped control the initial unwanted burst release. Including Na CMC increased eptifibatide entrapment from 75% to 95%. Trehalose helped prevent the degradation of eptifibatide during lyophilization, and including PVA and PEG-400 reduced the lag phase and led to a controlled-release profile. Thus, including additives in the formulation can effectively improve the drug load and address issues associated with biodegradable-polymer-based microspheres. Full article

Cyclodextrins (CDs) enhance the solubility of poorly water-soluble drugs like ibuprofen (IBU), making them promising carriers for pulmonary drug delivery. This route lowers the required dose, minimizing side effects, which could be beneficial in treating cystic fibrosis. In this study, a nano-spray-drying technique was applied to prepare CD/IBU complexes using sulfobutylether-β-cyclodextrin (SBECD) or (2-Hydroxy-3-N,N,N-trimethylamino)propyl-beta-cyclodextrin chloride (QABCD) as carriers as well as mannitol (MAN) and leucine (LEU) as aerosolization excipients. Various investigation techniques were utilized to examine and characterize the samples, including a Master Sizer particle size analyzer, scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and Fourier-transform infrared spectroscopy (FT-IR). We applied in vitro Andersen Cascade Impactor measurements and in silico simulation analysis to determine the sample’s aerodynamic properties. We also performed in vitro dissolution and diffusion tests. Applying formulations with optimal aerodynamic properties, we achieved an improved ~50% fine particle fraction values based on the Andersen Cascade Impactor measurements. The in vitro dissolution and diffusion studies revealed rapid IBU release from the formulations; however, the QABCD-based sample exhibited reduced membrane diffusion compared to SBECD due to the formation of electrostatic interactions. Full article

The low water solubility of an active pharmaceutical ingredient (aripiprazole) is one of the most critical challenges in pharmaceutical research and development. This antipsychotic drug has an inadequate therapeutic impact because of its minimal and idiosyncratic oral bioavailability to treat schizophrenia. The main objective of this study was to improve the solubility and stability of the antipsychotic drug aripiprazole (ARP) via forming binary as well as ternary inclusion complexes with hydroxypropyl-β-cyclodextrin (HPβCD) and L-Arginine (LA) as solubility enhancers. Physical mixing and lyophilization were used in different molar ratios. The developed formulations were analyzed by saturation solubility analysis, and dissolution studies were performed using the pedal method. The formulations were characterized by FTIR, XRD, DSC, SEM, and TGA. The results showcased that the addition of HPβCD and LA inclusion complexes enhanced the stability, in contrast to the binary formulations and ternary formulations prepared by physical mixing and solvent evaporation. Ternary formulation HLY47 improved dissolution rates by six times in simulated gastric fluid (SGF). However, the effect of LA on the solubility enhancement was concentration-dependent and showed optimal enhancement at the ratio of 1:1:0.27. FTIR spectra showed the bond shifting, which confirmed the formation of new complexes. The surface morphology of complexes in SEM studies showed the rough surface of lyophilization and solvent evaporation products, while physical mixing revealed a comparatively crystalline surface. The exothermic peaks in DSC diffractograms showed diminished peaks previously observed in the diffractogram of pure drug and LA. Lyophilized ternary complexes displayed significantly enhanced thermal stability, as observed from the thermograms of TGA. In conclusion, it was observed that the preparation method and a specific drug-to-polymer and amino acid ratio are critical for achieving high drug solubility and stability. These complexes seem to be promising candidates for novel drug delivery systems development. Full article

Flibanserin (FLB) is a drug used for female hypotensive sexual desire disorder approved by the FDA in August 2015. FLB exhibits extensive hepatic first-pass metabolism and low aqueous solubility, hence poor oral bioavailability. In this study, beta hydroxypropyl cyclodextrin-FLB inclusion complexes were incorporated into orally fast dissolving films. This dosage form was expected to improve FLB aqueous solubility, which would give fast onset of action and decrease presystemic metabolism, hence improving oral bioavailability. The inclusion complex at a ratio of 1:1 was prepared by the kneading method. Differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), and powder X-ray diffractometry (XRD) were used to confirm complex formation. The Box–Behnken design (15 different formulae of FLB fast-dissolving oral films (FLBFDOFs) were utilized for the optimization of the prepared films. The Expert Design 11 program was utilized to examine the effects of three selected factors, polymer concentration (X₁), plasticizer concentration (X₂), and disintegrant concentration (X₃) on four responses: disintegration time (DT), initial dissolution rate (IDR), dissolution efficiency (DE), and film quality (QF). Numerical optimization was performed by minimizing disintegration time (Y1), while maximizing the initial drug dissolution rate (Y₂), dissolution efficiency (Y₃), and the quality factor (Y₄). The statistical analysis showed that X₁ has a significant positive effect on the disintegration time and a significant negative effect on IDR. While X₂ and X₃ produced a nonsignificant negative effect on IDR. Dissolution efficiency was maximized at the middle concentration of both X₂ and X₃. The best film quality was observed at the middle concentration of both X₁ and X₂. In addition, increasing X₃ leads to an improvement in film quality. The optimized film cast from an aqueous solution contains hydroxypropyl cellulose (2%) as a hydrophilic film-forming agent and propylene glycol (0.8%) as a plasticizer and cross povidone (0.2%) as a disintegrant. The prepared film released 98% of FLB after 10 min and showed good physical and mechanical properties. The optimized formula showed a disintegration time of 30 s, IDR of 16.6% per minute, DE₁₅ of 77.7%, and QF of 90%. This dosage form is expected to partially avoid the pre-systemic metabolism with a fast onset of action, hence improving its bioavailability that favors an advantage over conventional dosage forms. Full article

In this study, hydroxypropyl-beta-cyclodextrin (HP-β-CD) particles were produced using supercritical assisted atomization (SAA) with carbon dioxide as the spraying medium or co-solute and aqueous ethanol solution as the solvent. The effects of several key factors on the morphology and size of the HP-β-CD particles were investigated. These factors included the solvent effect, temperatures of the precipitator and saturator, concentration of the HP-β-CD solution, and flow rate ratio of carbon dioxide to the HP-β-CD solution. The conducive conditions for producing fine spherical particles were 54.2% (w/w) aqueous ethanol as the solvent; precipitator and saturator temperatures of 373.2 K and 353.2 K, respectively; a flow rate ratio of carbon dioxide to HP-β-CD solution of 1.8; and low concentrations of HP-β-CD solution. The addition of leucine (LEU) enhanced the aerosol performance of the HP-β-CD particles, and the fine particle fraction (FPF) of the HP-β-CD particles with the addition of 13.0 mass% LEU was 1.8 times higher than that of the HP-β-CD particles without LEU. This study shows that LEU can act as a dispersion enhancer and that HP-β-CD particles produced using SAA can be used as pulmonary drug carriers. Full article