Advances in Polymer Design for Enhancing Oral Drug Solubility and Delivery

Abstract

Synthetic polymers have enabled amorphous solid dispersions (ASDs) to emerge as an oral delivery strategy for overcoming poor drug solubility in aqueous environments. Modern ASD products noninvasively treat a range of chronic diseases (for example, hepatitis C, cystic fibrosis, and HIV). In such formulations, polymeric carriers generate and maintain drug supersaturation upon dissolution, increasing the apparent drug solubility to enhance gastrointestinal barrier absorption and oral bioavailability. In this Review, we outline several approaches in designing polymeric excipients to drive interactions with active pharmaceutical ingredients (APIs) in spray-dried ASDs, highlighting polymer-drug formulation guidelines from industrial and academic perspectives. Special attention is given to new commercial and specialized polymer design strategies that can solubilize highly hydrophobic APIs and suppress the propensity for rapid drug recrystallization. These molecularly customized excipients and hierarchical excipient assemblies are promising toward informing early-stage drug-discovery development and reformulating existing API candidates into potentially lifesaving oral medicines for our growing global population.

Preparation of Puerarin Chitosan Oral Nanoparticles by Ionic Gelation Method and Its Related Kinetics

“…Nanoparticles (NPs), as a new generation of submicron-sized drug delivery systems, have the advantages of controlling drug release, avoiding drug degradation or leakage, good targeting, and improving bioavailability, among other advantages. Nanoparticle-based drug delivery systems are a research hotspot for new drug delivery technologies and new dosage forms [16].…”

Biotin-functionalized copolymeric PEG-PCL micelles for in vivo tumour-targeted delivery of artemisinin

“…With the structure of amphiphilic polymeric micelles, hydrophobic drug compounds are soluble within the hydrophobic nuclei, while the shell retains a hydration barrier that protects the integrity of each microcell [5,6]. As a result, polymeric micelles can be used as efficient containers for undesired solvents with low stability in physiological environments [7,8]. Additionally, the ability to categorize multiple groups provides a significant scope for accurately adjusting drug loading and drug-targeted propagation properties.…”

Combining Surface Templating and Confinement for Controlling Pharmaceutical Crystallization

“…Typically, commercially available amorphous forms of APIs are prepared in conjunction with polymeric excipients, such as polyvinylpyrrolidone (PVP) and hydroxypropyl methylcellulose (HPMC), in order to prevent crystallization and increase bioavailability [ 15 , 45 , 46 , 47 ]. The amorphous form may be produced in a combined confinement and surface templating precipitation process, similar to the crystal forms that are the focus of this review, but it is more desirable to have molecular level mixing of the amorphous form with the polymer excipient for stability [ 48 , 49 , 50 , 51 ], so this is not a focus of the combined confinement and surface templating studies.…”

“…Frequently, for class 2 and class 4 drugs (low solubility), the required clinical dosage of a drug is insoluble in physiological amounts of gastrointestinal fluid, rendering the drug inaccessible to the body [ 3 ]. According to the U.S. Pharmacopoeia, solubilities below 10 mg/mL are considered sparingly soluble and under 0.1 mg/mL are practically insoluble [ 3 , 15 , 16 ]. To dissolve some of these drugs such as piroxicam, a pain medication, over 2 L of GI fluid would be required [ 13 ].…”