Enhanced and Prolonged Immunogenicity in Mice of Thermally Stabilized Fatty Acid-Conjugated Vaccine Antigen.

Background/objectives: Influenza vaccines require good thermal stability without the need for refrigerator storage. Although the fatty acid-conjugated hemagglutinin (Heg) vaccine antigen provides good stability in both solid and liquid states, its therapeutic effectiveness must be validated in vivo. This study aimed to investigate the immunogenicity of the thermally stabilized Heg-oleic acid conjugate (HOC) and compare it with native Heg as a reference.

Release-modulating mechanism and comparative pharmacokinetics in beagle dogs of bethanechol-loaded oral dosage forms.

Bethanechol chloride (BTC), a quaternary ammonium compound used in bladder dysfunction treatment, requires challenges in developing optimal oral dosage forms due to its high water-solubility, short half-life, rapid elimination and four times a day administration. The aim of this study was to develop optimal BTC-loaded oral dosage forms that could provide both rapid onset and sustained therapeutic effects while reducing the frequency of conventional four-times-daily dosing (Mytonin® tablets). Four different BTC-loaded oral dosage forms were designed including gastro-retentive tablet (GRT), controlled-release tablet (CRT), bilayer tablet (BLT), and tablet-in-tablet (TIT).

Novel First-Generation Dissolution Models to Investigate the Release and Uptake of Oral Lymphotropic Drug Products.

Conventional dissolution tests only assess the aqueous release of drugs to ensure quality and performance, without indicating whether absorption occurs through the portal or the lymphatic circulation. To address this issue, this study aimed to develop novel first-generation dissolution models that could investigate the release and uptake of oral lymphotropic drugs and examine relevant formulation issues. Dissolution of three commercial lymphotropic drug products (Terbinafina, Apo-terbinafine, and Lamisil) was done using modified versions of USP Apparatus II and IV.

In Vitro Predictive Model for Intestinal Lymphatic Uptake: Exploration of Additional Enhancers and Inhibitors.

Drug absorption via chylomicrons holds significant implications for both pharmacokinetics and pharmacodynamics. However, a mechanistic understanding of predicting in vivo intestinal lymphatic uptake remains largely unexplored. This study aimed to delve into the intestinal lymphatic uptake of drugs, investigating both enhancement and inhibition using various excipients through our previously established in vitro model.

Self-assembled nanonization of fatty acid-conjugated vaccine antigen for enhanced thermal stability.

The aim of this study was to evaluate the enhanced thermal stability and physicochemical properties of fattigated vaccine antigens. High molecular weight influenza hemagglutinin (Heg) was used as a model antigen because of low heat stability requiring cold chamber. Heg was conjugated with long-chain oleic acid (C18) and short-chain 3-decenoic acid (C10) to prepare fattigated Heg.

Nanonization and Deformable Behavior of Fattigated Peptide Drug in Mucoadhesive Buccal Films.

This study was tasked with the design of mucoadhesive buccal films (MBFs) containing a peptide drug, leuprolide (LEU), or its diverse nanoparticles (NPs), for enhanced membrane permeability via self-assembled nanonization and deformable behavior. An LEU-oleic acid conjugate (LOC) and its self-assembled NPs (LON) were developed. Additionally, a deformable variant of LON (d-LON) was originally developed by incorporating l-α-phosphatidylcholine into LON as an edge activator.

Polyelectrolyte-based solid dispersions for enhanced dissolution and pH-Independent controlled release of sildenafil citrate.

The aim of this study was to design a novel matrix tablet with enhanced dissolution and pH-independent controlled release of sildenafil citrate (SIL), a drug with pH-dependent solubility, by using solid dispersions (SDs) and polyelectrostatic interactions. SIL-loaded SDs were prepared using various polymeric carriers such as poloxamer 188, poloxamer 407, Soluplus®, polyvinylpyrrolidone (PVP) K 12, and PVP K 17 by the solvent evaporation method. Among these polymers, Soluplus® was found to be the most effective in SDs for enhancing the drug dissolution over 6 h in pH 6.

Investigation of Cannabinoid Acid/Cyclodextrin Inclusion Complex for Improving Physicochemical and Biological Performance.

This study aimed to investigate the enhancement of cannabinoid acid solubility and stability through the formation of a cannabinoid acid/cyclodextrin (CD) inclusion complex. Two cannabinoid acids, tetrahydro-cannabinolic acid (THCA) and cannabidiolic acid (CBDA), were selected as a model drug along with five types of CD: α-cyclodextrin (α-CD), β-cyclodextrin (β-CD), γ-cyclodextrin (γ-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD), and methylated-β-cyclodextrin (M-β-CD). Phase solubility studies were conducted using various types of CD to determine the complex stoichiometry.

Development of a Novel In Vitro Model to Study Lymphatic Uptake of Drugs via Artificial Chylomicrons.

The lymphatic system plays a crucial role in the absorption of lipophilic drugs, making it an important route for drug delivery. In this study, an in vitro model using Intralipid was developed to investigate the lymphatic uptake of drugs. The model was validated using cannabidiol, halofantrine, quercetin, and rifampicin.

Cellular Efficacy of Fattigated Nanoparticles and Real-Time ROS Occurrence Using Microfluidic Hepatocarcinoma Chip System: Effect of Anticancer Drug Solubility and Shear Stress.

The objective of this study was to evaluate the effectiveness of organ-on-chip system investigating simultaneous cellular efficacy and real-time reactive oxygen species (ROS) occurrence of anticancer drug-loaded nanoparticles (NPs) using hepatocarcinoma cells (HepG2) chip system under static and hepatomimicking shear stress conditions (5 dyne/cm). Then, the role of hepatomimetic shear stress exposed to HepG2 and drug solubility were compared. The highly soluble doxorubicin (DOX) and poorly soluble paclitaxel (PTX) were chosen.

Physicochemical and Biopharmaceutical Controllability of New Self-Assembled Fatty Acid Conjugated Leuprolide for the Enhanced Anticancer Activity.

Background: Leuprolide (LEU), a synthetic nonapeptide analog of naturally occurring gonadotropin-releasing hormone (GnRH), could exert a direct inhibitory activity on the proliferation of prostate cancer cells. However, the short half-life in blood and the biopharmaceutical problem of LEU limit this anticancer activity.

Purpose: To improve its druggability for improving anticancer activity, the amine-group targeted LEU was conjugated with different chain lengths of saturated fatty acids (FAs).

Mucoadhesive buccal tablet of leuprolide and its fatty acid conjugate: Design, in vitro evaluation and formulation strategies.

This study aimed to design mucoadhesive buccal tablets of leuprolide (LEU) and to manufacture and evaluate the properties of buccal tablets containing LEU-oleic acid conjugate (LOC) and self-assembled LEU-oleic acid nanoparticles (LON), which were developed in a previous study. Hydroxypropyl methylcellulose (HPMC 4000) was used as the mucoadhesive polymer, and tablets were prepared by direct compression. The formulations were characterized by weight, content uniformity, thickness, hardness, swelling index, disintegration time, mucoadhesion time, and drug release.

Dual thermal stabilizing effects of xanthan gums via glycosylation and hydrogen bonding and in vivo human bioavailability of desmopressin in orodispersible film.

Desmopressin acetate (DDAVP), a nonapeptide drug, is easily destroyed by heat in the manufacturing process of orodispersible film (ODF). A new challenging study was conducted to improve thermal stability through glycosylation and hydrogen bonding using carbohydrate gums (agar, arabic gum, carrageenan, xanthan gum) using the solvent casting method. Among gum types, xanthan gum strongly showed dual stabilizing effects of DDAVP via covalent glycosylation and hydrogen bonding, minimizing total impurities and optimizing physicochemical properties of ODF under accelerated conditions for six months.

Sub-cellular sequestration of alkaline drugs in lysosomes: new insights for pharmaceutical development of lysosomal fluid.

Background And Purpose: Lysosomal-targeted drug delivery can open a new strategy for drug therapy. However, there is currently no universally accepted simulated or artificial lysosomal fluid utilized in the pharmaceutical industry or recognized by the United States Pharmacopeia (USP).

Experimental Procedure: We prepared a simulated lysosomal fluid (SLYF) and compared its composition to a commercial artificial counterpart.

Biphasic dissolution combined with modified cylinder method-A new promising method for dissolution test in drug-loaded nanoemulsions.

Dissolution testing is important in assessing the in vitro drug release performance for oral administration dosage forms. However, currently, a simple and efficient in vitro test to investigate critical factors that may impact the drug release and bioavailability at the development stage of a drug-loaded nanoemulsion (NE) is lacking. Thus, in this study, we developed a new combined biphasic and modified cylinder (BP + MC) method to evaluate the dissolution profile of NEs.

Investigation of Patient-Centric 3D-Printed Orodispersible Films Containing Amorphous Aripiprazole.

The objective of this study was to design and evaluate an orodispersible film (ODF) composed of aripiprazole (ARP), prepared using a conventional solvent casting technique, and to fuse a three-dimensional (3D) printing technique with a hot-melt extrusion (HME) filament. Klucel LF (hydroxypropyl cellulose, HPC) and PE-05JPS (polyvinyl alcohol, PVA) were used as backbone polymers for 3D printing and solvent casting. HPC-, PVA-, and ARP-loaded filaments were applied for 3D printing using HME.

Design and evaluation of in vivo bioavailability in beagle dogs of bilayer tablet consisting of immediate release nanosuspension and sustained release layers of rebamipide.

The purpose of this study was to develop a once-daily, bilayer matrix tablet with immediate (IR) and sustained release (SR) layers of poorly water-soluble and absorption site dependent rebamipide (RBM) to substitute three times a day IR tablet. Owing to the pH-dependent poor water solubility of RBM in low pH condition, salt-caged nanosuspensions (NSPs) consisting of RBM and poloxamer 407 (POX 407) or poloxamer 188 (POX 188) were prepared using an acid-base neutralization method to increase the dissolution rate, which was subsequently applied to the immediate-release (IR) layer. Polyethylene oxide (PEO) with different molecular weights (PEO 100,000 and PEO 5,000,000) and hydroxypropyl methylcellulose 4000 (HPMC 4000) were then investigated as SR agents to incorporate into the SR layer with pure RBM via wet granulation method.

In Vitro Evaluation of a Foamable Microemulsion Towards an Improved Topical Delivery of Diclofenac Sodium.

Topical microemulsion (ME) might provide a novel and advanced transdermal delivery system due to the enhances of drug solubility and permeability across the stratum corneum. Foams are topical delivery systems that have excellent patient compliance, acceptability, and preference. Therefore, this study aimed to investigate a foamable microemulsion as an alternative topical and transdermal dosage form for diclofenac sodium (DS).

Electrostatic molecular effect of differently charged surfactants on the solubilization capacity and physicochemical properties of salt-caged nanosuspensions containing pH-dependent and poorly water-soluble rebamipide.

In this study, the electrostatic molecular effect of differently charged surfactants on the solubilization capacity and physicochemical properties of salt-caged nanosuspensions (NSPs) containing poorly water-soluble drug was investigated. Anionic rebamipide (RBM) was chosen as a model drug because of its poor water solubility in low pH condition and ionizable acidic forms. Negatively charged sodium lauryl sulfate (SLS) and positively charged cetyltrimethylammonium bromide (CTAB) were selected as surfactants for the preparation of NSPs or in the dissolution medium.

Improved Bioavailability of Poorly Water-Soluble Drug by Targeting Increased Absorption through Solubility Enhancement and Precipitation Inhibition.

Itraconazole (ITZ) is a class II drug according to the biopharmaceutical classification system. Its solubility is pH 3-dependent, and it is poorly water-soluble. Its pKa is 3.

Modulation of the clinically accessible gelation time using glucono-d-lactone and pyridoxal 5'-phosphate for long-acting alginate in situ forming gel injectable.

The purpose of this study was to design alginate in situ forming gel (ISFG) injectable with clinically acceptable gelation time and controlled release of hydrophobic drug. Milled or unmilled paliperidone palmitate (PPP) was used. The gelation time was controlled by varying the ratios of glucono-d-lactone (GDL) and pyridoxal 5'-phosphate (PLP) in prefilled alginate solution mixtures (ASMs) containing PPP, CaCO, GDL and PLP for clinically acceptable injectability.

Development of a novel cannabinoid-loaded microemulsion towards an improved stability and transdermal delivery.

The aim of this study was to develop a stable microemulsion (ME) for transdermal delivery of tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA). The lipid-based vehicles were selected by screening cannabinoid solubility and the emulsifying ability of surfactants. Pseudo-ternary phase diagrams were constructed by formulation of cannabinoids with Capryol® 90 as oil phase, Tween® 80, Solutol® HS15, Procetyl® AWS, and Cremophor® RH40 as surfactants, ethanol as cosurfactant, and distilled water as the aqueous phase.

Role of Surfactant Micellization for Enhanced Dissolution of Poorly Water-Soluble Cilostazol Using Poloxamer 407-Based Solid Dispersion via the Anti-Solvent Method.

This study aimed to investigate the role of micellization of sodium lauryl sulfate (SLS) in poloxamer 407 (POX)-based solid dispersions (POX-based SDs) using the anti-solvent method in enhancing the dissolution rate of practically water-insoluble cilostazol (CLT). Herein, SLS was incorporated into CLT-loaded SDs, at a weight ratio of 50:50:10 of CLT, POX, and SLS by three different methods: anti-solvent, fusion (60 °C), and solvent (ethanol) evaporation. The SDs containing micellar SLS in the anti-solvent method were superior in the transformation of the crystalline form of the drug into a partial amorphous state.

Evaluation of the impact of abuse deterring agents on the physicochemical factors of tramadol-loaded tablet and the definition of new abuse deterrent index.

In the design of abuse-deterrent formulations (ADFs), pharmaceutical strategies that do not modify the physical and chemical properties of opioid dosage forms should be investigated. Among these, four major drug abusing factors, including particle size by physical modification, swellability, dissolution rate, and solvent extraction, were mainly characterized for evaluating abuse deterrence of narcotics. Tramadol hydrochloride (TMD) was chosen as a model drug.