pH-sensitive polymeric nanoparticles to improve oral bioavailability of peptide/protein drugs and poorly water-soluble drugs

Abstract Low oral bioavailability as a consequence of low water solubility of drugs is a growing challenge to the development of new pharmaceutical products. One of the most popular approaches of oral bioavailability and solubility enhancement is the utilization of lipid-based drug delivery systems. Their use in product development is growing due to the versatility of pharmaceutical lipid excipients and drug formulations, and their compatibility with liquid, semi-solid, and solid dosage forms. Lipid formulations, such as self-emulsifying (SEDDS), self-microemulsifying SMEDDS) and self- -nanoemulsifying drug delivery systems (SNEDDS) were explored in many studies as an efficient approach for improving the bioavailability and dissolution rate of poorly water-soluble drugs. One of the greatest advantages of incorporating poorly soluble drugs into such formulations is their spontaneous emulsification and formation of an emulsion, microemulsion or nanoemulsion in aqueous media. This review article focuses on the following topics. First, it presents a classification overview of lipid-based drug delivery systems and mechanisms involved in improving the solubility and bioavailability of poorly water-soluble drugs. Second, the article reviews components of lipid-based drug delivery systems for oral use with their characteristics. Third, it brings a detailed description of SEDDS, SMEDDS and SNEDDS, which are very often misused in literature, with special emphasis on the comparison between microemulsions and nanoemulsions.

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NOVEL APPLICATION OF MIXED HYDROTROPIC SOLUBILIZATION TECHNIQUE IN THE FORMULATION AND EVALUATION OF SOLID DISPERSION OF FLUPIRTINE MALEATE

Journal of Drug Delivery and Therapeutics ◽

10.22270/jddt.v8i5.1911 ◽

2018 ◽

Vol 8 (5) ◽

pp. 481-488

Author(s):

Nisha Kumari Yadav ◽

Tripti Shukla ◽

Neeraj Upmanyu ◽

Sharad Prakash Pandey ◽

Mohammad Azaz Khan

Keyword(s):

Particle Size ◽

Solid Dispersion ◽

Sodium Benzoate ◽

Oral Bioavailability ◽

Solid Dispersions ◽

Water Soluble ◽

Poorly Water Soluble Drugs ◽

Water Soluble Drugs ◽

Evaporation Technique ◽

Poorly Water Soluble

Flupirtine is an amino pyridine derivative that functions as a centrally acting non-opioid, non-steroidal analgesic. It is a selective neuronal potassium channel opener that also has NMDA receptor antagonist properties. Its muscle relaxant properties make it popular for back pain and other orthopedics uses. In the present investigation, recently developed mixed hydrotropic solid dispersion technology precludes the use of organic solvent and also decreases the individual concentration of hydrotropic agents, simultaneously decreasing their toxic potential. Mixed-hydrotropic solubilisation technique is the experience to increase the solubility of poorly water soluble drugs in the aqueous solution containing blends of hydrotropic agents, which may give synergistic enhancement effect on solubility of poorly water-soluble drugs and to reduce concentrations of each individual hydrotropic agent to minimize their toxic effects due to high concentration of hydrotropic agents. The Flupirtine loaded solid dispersion was prepared by a solvent evaporation technique using sodium benzoate and a niacinamide hydrotropic mixture. The prepared solid dispersions were valuated regarding their solubility, mean particle size, in-vitro drug release. The prepared solid dispersions were found very stable (chemically). The superior dissolution rate due to its reduced particle size may have contributed to the increased oral bioavailability. This study demonstrated that mixed-solvency may be an alternative approach for poorly soluble drugs to improve their solubility and oral bioavailability. Keywords: Flupirtine, Solid dispersion, Mixed-hydrotropic solubilisation, Solvent evaporation technique, Sodium benzoate, Niacinamide

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Impact of surface area of silica particles on dissolution rate and oral bioavailability of poorly water soluble drugs: A case study with aceclofenac

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2013.12.017 ◽

2014 ◽

Vol 461 (1-2) ◽

pp. 459-468 ◽

Cited By ~ 38

Author(s):

Dinesh Kumar ◽

S.V. Sailaja Chirravuri ◽

Nalini R. Shastri

Keyword(s):

Dissolution Rate ◽

Surface Area ◽

Oral Bioavailability ◽

Silica Particles ◽

Water Soluble ◽

Poorly Water Soluble Drugs ◽

Water Soluble Drugs ◽

Poorly Water Soluble

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The effect of drug ionization on lipid-lased formulations for the oral delivery of anti-psychotics

ADMET & DMPK ◽

10.5599/admet.830 ◽

2020 ◽

Author(s):

Tahlia R Meola ◽

Kara Paxton ◽

Paul Joyce ◽

Hayley B Schultz ◽

Clive A Prestidge

Keyword(s):

Oral Bioavailability ◽

Oral Delivery ◽

Fold Increase ◽

Water Soluble ◽

Equilibrium Solubility ◽

Poorly Water Soluble Drugs ◽

Physiochemical Properties ◽

Water Soluble Drugs ◽

Poorly Water Soluble ◽

Rate Limiting

<p class="ADMETabstracttext">Lipid-based formulations (LBFs) are well-known to improve the oral bioavailability of poorly water-soluble drugs (PWSDs) by presenting the drug to the gastrointestinal environment in a molecularly dispersed state, thus avoiding the rate-limiting dissolution step. Risperidone and lurasidone are antipsychotics drugs which experience erratic and variable absorption, leading to a low oral bioavailability. The aim of this research was to develop and investigate the performance of risperidone and lurasidone when formulated as an emulsion and silica-lipid hybrid (SLH). Lurasidone and risperidone were dissolved in Capmul® MCM at 100% and 80% their equilibrium solubility, respectively, prior to forming a sub-micron emulsion. SLH microparticles were fabricated by spray-drying a silica stabilised sub-micron emulsion to form a solid powder. The performances of the formulations were evaluated in simulated intestinal media under digesting conditions, where the emulsion and SLH provided a 17-fold and 23-fold increase in LUR solubilisation, respectively. However, the performance of RIS was reduced by 2.2-fold when encapsulated within SLH compared to pure drug. Owing to its pKa, RIS adsorbed to the silica and thus, dissolution was significantly hindered. The results reveal that LBFs may not overcome the challenges of all PWSDs and physiochemical properties must be carefully considered when predicting drug performance.</p>

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