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

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Abstract

Although oral drug delivery is considered as most acceptable route for administering the active pharmaceutical ingredients to patients of all age-groups with the exceptions of bed-ridden patients and infants, the extent and rate of drug reaching the systemic circulation (in other word, drug bioavailability) always depends on many factors such as drug solubility in gastrointestinal fluids and drug permeation into intraluminal epithelial membrane structure, absence (fasting state) and presence (fed state) of food materials in the gastrointestinal tract, and individual variations in gastric emptying time. Taking the most influential factors like drug solubility and its permeability into consideration, these two factors play a pivotal role and even act as the litmus test for the formulation scientists who involve in oral dosage form development. It is very clear that there should be an optimum solubility and permeability balance to be reachable for getting the desired drug bioavailability to exert the intended therapeutic activity. The objectives of current review are (1) to provide an overview of two-different categories of poorly water soluble API molecules, (2) to describe briefly three-different case studies taken from drug solubility-enhancing formulations dealing with interplay between solubility and permeability, and (3) to showcase selected examples of solubility-permeability interplay phenomena arising out from the various orally administrable dosage forms. The lessons learnt from the past and current literatures are certainly encouraging to go ahead for oral dosage form development but with the prior knowledge about the possible existence of solubility-permeability interplay/tradeoff phenomenon.

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Abbreviations

ABA:

Amino benzoic acid

AI:

Artificial intelligence

ANN:

Artificial neural network

APIs:

Active pharmaceutical ingredients

ASD:

Aqueous solid dispersion

BCS:

Biopharmaceutics classification system

CNZ:

Cinnarizine

DCS:

Developability classification system

EPO:

Methacrylate copolymer Eudragit

FB:

Fenofibrate

GSE:

General solubility equation (GSE)

HPMC:

Hydroxypropyl methylcellulose

HTS:

High-throughput screening

ML:

Machine learning

OSPB:

Optimal solubility permeability balance

PAMPA:

Parallel artificial membrane permeability assay

PVP:

Polyvinylpyrrolidone

SBE:

Sulfobutylether

S-SMEDDS:

Solid-self microemulsifying drug delivery system

S-SNEDDS:

Solid self nanoemulsifying drug delivery system

Tm:

Melting point

TPGS:

Tocopheryl polyethylene glycol (1000) succinate

UWL:

Unstirred water layer

WW:

Working window

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Acknowledgements

The author Datta Maroti Pawde would like to thank the National Mission on Himalayan Studies (NMHS), Ministry of Environment, Forest & Climate Change (MoEF & CC) Nodal and Serving hub with G.B. Pant National Institute of Himalayan Environment & Sustainable Development, Govt. of India for providing the financial support.

Funding

This study received funding provided by the Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Govt. of India to the authors Bhakti Mahendra Pawar, Syed Nazrin Ruhina Rahman and Abhinab Goswami.

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Authors and Affiliations

  1. Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER)-Guwahati, C/O SilaKatamur (Halugurisuk), Changsari, Kamrup, Guwahati, Assam, India

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

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  1. Bhakti Mahendra Pawar
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Correspondence to Tamilvanan Shunmugaperumal.

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Pawar, B.M., Rahman, S.N.R., Pawde, D.M. et al. Orally Administered Drug Solubility-Enhancing Formulations: Lesson Learnt from Optimum Solubility-Permeability Balance. AAPS PharmSciTech 22, 63 (2021). https://doi.org/10.1208/s12249-021-01936-9

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