Orally Administered Drug Solubility-Enhancing Formulations: Lesson Learnt from Optimum Solubility-Permeability Balance

Pawar, Bhakti; Rahman, Syed Nazrin Ruhina; Pawde, Datta Maroti; Goswami, Abhinab; Shunmugaperumal, Tamilvanan

doi:10.1208/s12249-021-01936-9

Cited by 10 publications

(8 citation statements)

References 38 publications

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“…Although various solubility-enabling formulations can be applied to the development of oral dosage forms, most of the pharmaceutical excipients (e.g., cosolvents, cyclodextrins, surfactants, hydrotropes, etc.) may affect the permeability in opposite directions [ 43 , 44 ]. However, its drug permeability impact depends on the amount of excipient used.…”

Section: Resultsmentioning

confidence: 99%

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Improvement in Solubility–Permeability Interplay of Psoralens from Brosimum gaudichaudii Plant Extract upon Complexation with Hydroxypropyl-β-cyclodextrin

Machado

Silva

et al. 2022

Molecules

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Psoralen (PSO) and 5-methoxypsoralen (5-MOP) are widely used drugs in oral photochemotherapy against vitiligo and major bioactive components of root bark extract of Brosimum gaudichaudii Trécul (EBGT), previously standardized by LC-MS. However, the exceptionally low water solubility of these psoralens can cause incomplete and variable bioavailability limiting their applications and patient adherence to treatment. Therefore, the purpose of this work was to investigate the effects of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complex on the solubility and jejunal permeability of PSO and 5-MOP from EBGT. Characterization of inclusion complexes were evaluated by current methods in nuclear magnetic resonance studies on aqueous solution, Fourier transform infrared spectroscopy, thermal analysis, and scanning electron microscopy in solid state. Ex vivo rat jejunal permeability was also investigated and compared for both pure psoralens and plant extract formulation over a wide HP-β-CD concentration range (2.5 to 70 mM). Phase solubility studies of the PSO- and 5-MOP-HP-β-CD inclusion complex showed 1:1 inclusion complex formation with small stability constants (Kc < 500 M−1). PSO and 5-MOP permeability rate decreased after adding HP-β-CD by 6- and 4-fold for pure standards and EBGT markers, respectively. Nevertheless, the complexation with HP-β-CD significantly improved solubility of PSO (until 10-fold) and 5-MOP (until 31-fold). As a result, the permeability drop could be overcome by solubility augmentation, implying that the HP-β-CD inclusion complexes with PSO, 5-MOP, or EBGT can be a valuable tool for designing and developing novel oral drug product formulation containing these psoralens for the treatment of vitiligo.

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Section: Resultsmentioning

confidence: 99%

“…The primary approach to overcome this issue is using the minimal excipient amounts sufficient to dissolve the drug dose throughout the GIT. In other words, when the intrinsic permeability of the drug is very high, it may be useful to waste some permeability to gain solubility [ 43 , 45 ].…”

Section: Resultsmentioning

confidence: 99%

Improvement in Solubility–Permeability Interplay of Psoralens from Brosimum gaudichaudii Plant Extract upon Complexation with Hydroxypropyl-β-cyclodextrin

Machado

Silva

et al. 2022

Molecules

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“…Consequently, optimizing the API's solubility, dissolution rate, and permeability becomes crucial when developing oral dosage forms, as more than 50% of drug molecules are administered in tablet form. [5][6][7][8][9] Various approaches have been developed to modulate these properties, including screening for polymorphs, [10][11][12] amorphization, 13,14 forming solvates, [15][16][17] hydrates, [18][19][20][21] salts, [22][23][24][25] and co-crystals. [26][27][28][29] Among these methods, salt formation emerges as the most conventional approach for altering the solid-state characteristics of APIs.…”

Section: Introductionmentioning

confidence: 99%

Novel molecular adducts of an anti-cancer drug vandetanib with enhanced solubility

Bandaru,

Giri,

Krishna

et al. 2024

CrystEngComm

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“…For poorly permeable drugs, permeation enhancers are commonly used [8][9][10][11], for example, fatty alcohols, which increase drug permeability by altering the structure and properties of biofilms. Co-solvents could provide a way to address the issue of insoluble drugs, but they also lead to change in permeability [12]. SBE-β-CD [13][14][15][16][17][18], a new pharmaceutical excipient often used as a co-solvent, has been included in USP44-NF39 under the name Betadex Sulfobutyl Ether Sodium, and is currently available as Captisol ® [19,20] and Dexolve ® [21].…”

Section: Introductionmentioning

confidence: 99%

Decreased Penetration Mechanism of Ranitidine Due to Application of Sodium Sulfobutyl Ether-β-Cyclodextrin

Yang,

Zhang,

Huang

et al. 2023

Pharmaceutics

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Permeability has an important effect on drug absorption. In this study, the effect of different concentrations of sodium sulfobutyl ether-β-cyclodextrin (SBE-β-CD) on the absorption of ranitidine was investigated to examine the mechanism of permeability changes. The results of a parallel artificial membrane permeability assay (PAMPA) showed that increasing the concentration of sodium sulfobutyl ether-β-cyclodextrin, 0, 0.12% (w/v), 0.36% (w/v) and 3.6% (w/v), respectively, caused the apparent permeability coefficient of ranitidine to decrease to 4.62 × 10−5, 4.5 × 10−5, 3.61 × 10−5 and 1.08 × 10−5 in Caco-2 cells, respectively. The same results were obtained from an oral pharmacokinetic study in rats. Further studies indicated that SBE-β-CD significantly increased the zeta potential of ranitidine. SBE-β-CD interacted with ranitidine charges to form a complex that reduced ranitidine permeability, and SBE-β-CD should be chosen with caution for drugs with poor permeability.

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Orally Administered Drug Solubility-Enhancing Formulations: Lesson Learnt from Optimum Solubility-Permeability Balance

Cited by 10 publications

References 38 publications

Improvement in Solubility–Permeability Interplay of Psoralens from Brosimum gaudichaudii Plant Extract upon Complexation with Hydroxypropyl-β-cyclodextrin

Improvement in Solubility–Permeability Interplay of Psoralens from Brosimum gaudichaudii Plant Extract upon Complexation with Hydroxypropyl-β-cyclodextrin

Novel molecular adducts of an anti-cancer drug vandetanib with enhanced solubility

Decreased Penetration Mechanism of Ranitidine Due to Application of Sodium Sulfobutyl Ether-β-Cyclodextrin

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