Feasibility of Using Gluconolactone, Trehalose and Hydroxy-Propyl Gamma Cyclodextrin to Enhance Bendroflumethiazide Dissolution Using Lyophilisation and Physical Mixing Techniques

Abstract

Purpose: Hydrophobic drugs are facing a major challenge in dissolution rate enhancement and solubility in aqueous solutions; therefore, a variety of methods have been used to improve dissolution rate and/or solubility of bendroflumethiazide as a model hydrophobic drug. Methods: In this study, two main methods (physical mixing and lyophilisation) were used with gluconolactone, hydroxyl propyl γ-ccyclodextrin, and trehalose to explore this challenge. Bendroflumethiazide, practically insoluble in water, was mixed with one of the three excipients gluconolactone, hydroxyl propyl γ-cyclodextrin, and trehalose in three different ratios 1:1, 1:2, 1:5. To the best of our knowledge, the dissolution of the drug has not been previously enhanced by using either these methods or any of the used excipients. Samples containing drug and each of the excipients were characterized via dissolution testing, Fourier Transform infra-red spectroscopy, differential scanning calorimetry, and scanning electron microscopy. Results: The used methods showed a significant enhancement in dug dissolution rate; physical mixing significantly, p < 0.05, increased the percentage of the drug released with time; for example, bendroflumethiazide dissolution in distilled water was improved from less than 20% to 99.79% within 90 min for physically mixed drug-cyclodextrin 1:5. The lyophilisation process was enhanced and the drug dissolution rate and the highest drug dissolution was achieved for (drug-gluconolactone 1:1) with 98.98% drug release within 90 min. Conclusions: the physical mixing and freeze drying processes significantly increased the percentage of drug release with time.

Assessment of Various Food Proteins as Structural Materials for Delivery of Hydrophobic Polyphenols Using a Novel Co-Precipitation Method

“…In the present study, this was also confirmed in the case of the dispersibility of the polyphenols precipitated in the absence of any protein and the presence or absence of trehalose (see Figure S3). Such a beneficial effect of trehalose has also been reported in other studies, such as those reported by Saleh et al [45]. They [45] analyzed the effect of two methods (physical mixing and lyophilization) in combination with trehalose, gluconolactone, and hydroxyl propyl γ-cyclodextrin on the dissolution of bendroflumethiazide.…”

“…effect of trehalose has also been reported in other studies, such as those reported by Saleh et al [45]. They [45] analyzed the effect of two methods (physical mixing and lyophilization) in combination with trehalose, gluconolactone, and hydroxyl propyl γ-cyclodextrin on the dissolution of bendroflumethiazide.…”

“…They [45] analyzed the effect of two methods (physical mixing and lyophilization) in combination with trehalose, gluconolactone, and hydroxyl propyl γ-cyclodextrin on the dissolution of bendroflumethiazide. The authors stated that the dissolution enhancements for bendroflumethiazide, which resulted from the addition of trehalose, showed a promising opportunity for other poorly soluble drugs [45]. We observe that different proteins have different effects on the solubility of a specific polyphenol.…”

Isolation of Itraconazole Nanostructured Microparticles via Spray Drying with Rational Selection of Optimum Base for Successful Reconstitution and Compaction

“…The glucose ring structure of TRE may be more effective at disrupting the hydrogen bonded water network during solubilization compared with the short-chain structure of MAN. Furthermore, recent studies have shown that TRE exhibited a drug solubilizing character when physically mixed with bendroflumethiazide, a poorly soluble molecule, and an improvement in drug dissolution properties was achieved (47). These properties of TRE, accompanied by its amorphous character, may explain the reason for greater ITR solubilization in the presence of TRE compared with MAN at 30 min (p = 0.001) (Fig.…”

Fast Dissolving of Ferulic Acid via Electrospun Ternary Amorphous Composites Produced by a Coaxial Process

“…Among the different kinds of strategies that have been broadly investigated to resolve this problem, drug solid dispersions (SDs) are some of the most promising ways with many commercial products [ 5 , 6 , 7 , 8 , 9 ]. New methods for creating new kinds of high-performance SDs are always desired and are thus becoming a rapidly developing branch of pharmaceutical technologies [ 10 , 11 , 12 , 13 , 14 , 15 ].…”