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Investigation into the Emerging Role of the Basic Amino Acid L-Lysine in Enhancing Solubility and Permeability of BCS Class II and BCS Class IV Drugs

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Abstract

Background

The search for a simple and scalable approach that can improve the two key biopharmaceutical processes (solubility and permeability) for BCS Class II and BCS Class IV has still been unmet need.

Purpose

In this study, L-lysine was investigated as a potential excipient to tackle problems with solubility and permeability. Bendazac (Class II); quercetin and rutin (Class IV) were employed.

Methods

Drugs-lysine complexes in 1:1 M ratios were prepared by co-precipitation and co-grinding; characterized for solubility, partition coefficient, DSC, FTIR, SEM, dissolution rate and permeability. Chemical stability of quercetin-lysine and rutin-lysine was studied by assessing antioxidant capacity using Trolox and CUPRAC assays.

Results and Conclusion

Drugs-lysine salt/complexes were confirmed. Solubility enhancement factors ranged from 68- to 433-fold increases and dissolution rates were also significantly enhanced by up to 6-times, compared with drugs alone. With the exception of rutin-lysine, Papp for bendazac-lysine and quercetin-lysine enhanced by 2.3- to 4-fold. Papp for quercetin (Class IV) benefited more than bendazac (Class II) when complexed with lysine. This study warrants the use of L-lysine as a promising excipient for enhanced solubility and permeability of Class II and Class IV, providing that the solubility of the drug is ensured at ‘the door step’ of absorption sites.

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Abbreviations

BCS:

Biopharmaceutics classification system

CUPRAC:

Cupric ion reducing antioxidant capacity

DSC:

Differential scanning calorimetry

FTIR:

Fourier transform infrared spectroscopy

Papp :

Apparent permeability coefficient

SEM:

Scanning electron microscopy

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Authors and Affiliations

  1. Pharmaceutics Department, Faculty of Pharmacy, Minia University, Minia, Egypt

    Hamdy Abdelkader & Zeinab Fathalla

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  1. Hamdy Abdelkader
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  2. Zeinab Fathalla
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Correspondence to Hamdy Abdelkader.

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Abdelkader, H., Fathalla, Z. Investigation into the Emerging Role of the Basic Amino Acid L-Lysine in Enhancing Solubility and Permeability of BCS Class II and BCS Class IV Drugs. Pharm Res 35, 160 (2018). https://doi.org/10.1007/s11095-018-2443-0

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