-
International Journal of Pharmaceutics Mar 2020
Topics: Drug Delivery Systems; Humans; Pharmaceutical Preparations; Solubility
PubMed: 31958490
DOI: 10.1016/j.ijpharm.2020.119055 -
Structure (London, England : 1993) Jun 2023Amino acid deletions are high-risk, high-reward mutations, yet structural consequences are poorly understood. In this issue of Structure, Woods et al. (2023)...
Amino acid deletions are high-risk, high-reward mutations, yet structural consequences are poorly understood. In this issue of Structure, Woods et al. (2023) individually deleted 65 residues from a small α-helical protein, structurally assayed the 17 soluble variants, and developed a computational model of deletion solubility combining Rosetta and AlphaFold2.
Topics: Proteins; Amino Acids; Mutation; Solubility
PubMed: 37267922
DOI: 10.1016/j.str.2023.05.005 -
Molecules (Basel, Switzerland) Aug 2020Lipid-soluble bioactives are important nutrients in foods. However, their addition in food formulations, is often limited by limited solubility and high tendency for... (Review)
Review
Lipid-soluble bioactives are important nutrients in foods. However, their addition in food formulations, is often limited by limited solubility and high tendency for oxidation. Lipid-soluble bioactives, such as vitamins A, E, D and K, carotenoids, polyunsaturated fatty acids (PUFA) and essential oils are generally dispersed in water-based solutions by homogenization. Among the different homogenization technologies available, nanoemulsions are one of the most promising. Accordingly, this review aims to summarize the most recent advances in nanoemulsion technology for the encapsulation of lipid-soluble bioactives. Modern approaches for producing nanoemulsion systems will be discussed. In addition, the challenges on the encapsulation of common food ingredients, including the physical and chemical stability of the nanoemulsion systems, will be also critically examined.
Topics: Algorithms; Drug Compounding; Drug Stability; Emulsions; Lipids; Models, Theoretical; Molecular Structure; Nanoparticles; Nanotechnology; Solubility
PubMed: 32878137
DOI: 10.3390/molecules25173966 -
Drug Development and Industrial Pharmacy Jul 2021The number of active pharmaceutical compounds from the biopharmaceutical classification system (BCS) belonging to Class II and IV have significantly increased in recent... (Review)
Review
The number of active pharmaceutical compounds from the biopharmaceutical classification system (BCS) belonging to Class II and IV have significantly increased in recent years. These compounds have high therapeutic potential but are difficult to formulate as oral dosage forms due to their poor aqueous solubility. The solubility and bioavailability of these poorly water-soluble compounds can be increased by various formulation approaches, such as amorphous solid dispersions (ASD), salt formation, complexations, etc. Out of these techniques, the ASD approach, where compounds are converted into amorphous form and embedded in the hydrophilic matrix, have been successfully used in many marketed preparations. The recent advancement of this ASD approach is the design of ternary solid dispersions (TSD), where an additional component is added to further improve their performance in terms of solubility, stability, and processability. This review discusses the classification, mechanism of performance improvement, preparation techniques, and characterizations for TSD.
Topics: Biological Availability; Pharmaceutical Preparations; Polymers; Solubility; Water
PubMed: 33818224
DOI: 10.1080/03639045.2021.1908342 -
International Journal of Pharmaceutics Jun 2021Nanosizing of pharmaceutical drug particles is one of the most important drug delivery platforms approaches for the commercial development of poorly water-soluble drug... (Review)
Review
Nanosizing of pharmaceutical drug particles is one of the most important drug delivery platforms approaches for the commercial development of poorly water-soluble drug molecules. Though nanosizing of drug particles has been proven to greatly enhance drugs dissolution rate and apparent solubility, nanosized materials have presented significant challenges for their formulation as solid dosage forms (e.g. tablets, capsules). This is due to the strong Van der Waals attraction forces between dry nanoparticles leading to aggregation, cohesion, and consequently poor flowability. In this review, the broad area of nanomedicines is overviewed with the primary focus on drug nanocrystals and the top-down and bottom-up methods used in their fabrication. The review also looks at how nanosuspensions of pharmaceutical drugs are generated and stabilised, followed by subsequent strategies for isolation of the nanoparticles. A perspective on the future outlook for drug nanocrystals is also presented.
Topics: Chemistry, Pharmaceutical; Drug Delivery Systems; Nanoparticles; Pharmaceutical Preparations; Solubility; Tablets; Technology, Pharmaceutical
PubMed: 33992712
DOI: 10.1016/j.ijpharm.2021.120708 -
Critical Reviews in Food Science and... 2022Amorphous solid products have recently gained a lot of attention as key solutions to improve the solubility and bioavailability of poorly soluble nutraceuticals. A pure... (Review)
Review
Amorphous solid products have recently gained a lot of attention as key solutions to improve the solubility and bioavailability of poorly soluble nutraceuticals. A pure amorphous drug is a high-energy form; physically/chemically unstable and so easily gets recrystallized into the less soluble crystalline form limiting solubility and bioavailability issues. Amorphous solid dispersion and co-amorphous are new formulation approach that stabilized unstable amorphous form through different mechanisms such as preventing mobility, high glass transition temperature and molecular interaction. Nutraceuticals have been received the utmost importance due to their health benefits. However, most of these compounds have been associated with poor oral bioavailability due to poor solubility, high lipophilicity, high melting point, poor permeability, degradability and rapid metabolism in the gastrointestinal tract (GIT) which limits its health benefits. This review provides us a systematic application of amorphous systems to the delivery of poorly soluble nutraceuticals, with the aim of overcoming their pharmacokinetic limitations and improved pharmacological potential. In particular, it describes the challenges associated with delivery of oral nutraceuticals, various methods involved in the preparation and characterization of amorphous systems and permeability enhancement of nutraceuticals are in detail.
Topics: Biological Availability; Dietary Supplements; Drug Stability; Pharmaceutical Preparations; Solubility
PubMed: 33103462
DOI: 10.1080/10408398.2020.1836607 -
Drug Development and Industrial Pharmacy Nov 2021Nanocrystal technology is a new way to increase the solubility and bioavailability of poorly soluble drugs. As an intermediate preparation technology, nanocrystals are... (Review)
Review
Nanocrystal technology is a new way to increase the solubility and bioavailability of poorly soluble drugs. As an intermediate preparation technology, nanocrystals are widely used in drug delivery for oral, venous, percutneous and inhalation administration, which exhibits a broad application prospect. By referring to the domestic anforeign literatures, this paper mainly reviews the preparation methods of nanocrystals for poorly soluble natural products and its application in the mucosal delivery for skin, eye, oral cavity and nasal cavity. This can provide the reference for the research and development of nanocrystal technology in natural product preparations.
Topics: Biological Availability; Drug Delivery Systems; Nanoparticles; Pharmaceutical Preparations; Solubility
PubMed: 35287534
DOI: 10.1080/03639045.2022.2053985 -
Expert Opinion on Drug Discovery Jun 2023Oral administration of poorly water-soluble drugs (PWSDs) is generally related to low bioavailability, leading to high drug doses, multiple side effects, and low patient... (Review)
Review
INTRODUCTION
Oral administration of poorly water-soluble drugs (PWSDs) is generally related to low bioavailability, leading to high drug doses, multiple side effects, and low patient compliance. Thus, different strategies have been developed to increase drug solubility and dissolution in the gastrointestinal tract, opening new venues for these drugs.
AREAS COVERED
This review outlines the current challenges in PWSD formulation development and the strategies to overcome the oral barriers and increase their solubility and bioavailability. Conventional strategies include altering crystalline and molecular structures and modifying oral solid dosage forms. In contrast, novel strategies comprise micro- and nanostructured systems. Recent representative studies involving how these strategies have improved the oral bioavailability of PWSDs were also reviewed and reported.
EXPERT OPINION
New approaches to enhance PWSD bioavailability have sought to improve water solubility and dissolution rates, drug protection by overcoming biological barriers, and increased absorption. Still, only a handful of studies have focused on quantifying the increase in bioavailability. Improving the oral bioavailability of PWSDs remains an exciting unexplored field of research and has become an important issue for successfully developing pharmaceutical products.
Topics: Humans; Pharmaceutical Preparations; Biological Availability; Water; Drug Delivery Systems; Administration, Oral; Solubility
PubMed: 37157841
DOI: 10.1080/17460441.2023.2211801 -
The AAPS Journal Dec 2022This manuscript represents the view of the Dissolution Working Group of the IQ Consortium on the challenges of and recommendations on solubility measurements and... (Review)
Review
This manuscript represents the view of the Dissolution Working Group of the IQ Consortium on the challenges of and recommendations on solubility measurements and development of dissolution methods for immediate release (IR) solid oral dosage forms formulated with amorphous solid dispersions. Nowadays, numerous compounds populate the industrial pipeline as promising drug candidates yet suffer from low aqueous solubility. In the oral drug product development process, solubility along with permeability is a key determinant to assure sufficient drug absorption along the intestinal tract. Formulating the drug candidate as an amorphous solid dispersion (ASD) is one potential option to address this issue. These formulations demonstrate the rapid onset of drug dissolution and can achieve supersaturated concentrations, which poses significant challenges to appropriately characterize solubility and develop quality control dissolution methods. This review strives to categorize the different dissolution and solubility challenges for ASD associated with 3 different topics: (i) definition of solubility and sink conditions for ASD dissolution, (ii) applications and development of non-sink dissolution (according to conventional definition) for ASD formulation screening and QC method development, and (iii) the advantages and disadvantages of using dissolution in detecting crystallinity in ASD formulations. Related to these challenges, successful examples of dissolution experiments in the context of control strategies are shared and may lead as an example for scientific consensus concerning dissolution testing of ASD.
Topics: Solubility; Crystallization; Drug Liberation
PubMed: 36513860
DOI: 10.1208/s12248-022-00760-8 -
Future Medicinal Chemistry Feb 2023Prodrug strategy is critical for innovative drug development. Structural modification is the most straightforward and effective method to develop prodrugs. Improving... (Review)
Review
Prodrug strategy is critical for innovative drug development. Structural modification is the most straightforward and effective method to develop prodrugs. Improving drug defects and optimizing the physical and chemical properties of a drug, such as lipophilicity and water solubility, changing the way of administration can be achieved through specific structural modification. Designing prodrugs by linking microenvironment-responsive groups to the prototype drugs is of great help in enhancing drug targeting. In the meantime, making connections between prodrugs and suitable drug delivery systems could realize drug loading increases, greater stability, bioavailability and drug release control. In this paper, lipidic, water-soluble, pH-responsive, redox-sensitive and enzyme-activatable prodrugs are reviewed on the basis of structural modification.
Topics: Prodrugs; Drug Delivery Systems; Solubility; Drug Liberation; Water
PubMed: 36946236
DOI: 10.4155/fmc-2022-0309