Pharmacokinetic Evaluation of a Novel Donepezil-Loaded Dissolving Microneedle Patch in Rats.

Research on the development of dissolving microneedles (DMNs) has focused on bolus drug delivery, with little attention on sustained release. Here, we evaluated the sustained release, absorption pattern, and effective drug permeation of a novel donepezil-loaded DMN patch through an in vivo investigation on rats. The applications of DMN patches to the shaved skin of rats for 1 week and 1 h were compared with oral donepezil administration to assess their sustained release capabilities.

Microneedle systems for delivering nucleic acid drugs.

Background: Nucleic acid-based gene therapy is a promising technology that has been used in various applications such as novel vaccination platforms for infectious/cancer diseases and cellular reprogramming because of its fast, specific, and effective properties. Despite its potential, the parenteral nucleic acid drug formulation exhibits instability and low efficacy due to various barriers, such as stability concerns related to its liquid state formulation, skin barriers, and endogenous nuclease degradation. As promising alternatives, many attempts have been made to perform nucleic acid delivery using a microneedle system.

Physicochemical characterization of dapagliflozin and its solid-state behavior in stress stability test.

As an active pharmaceutical ingredient, dapagliflozin propanediol monohydrate (D-PD) has been used in the solvated form consisting of dapagliflozin compounded with (S)-propylene glycol and monohydrate at a 1:1:1 ratio. However, dapagliflozin propanediol loses the solvent's reduced lattice structure at slightly higher temperatures. Due to its sensitive solid-state stability, the temperature and humidity are strictly controlled during the production and storage of dapagliflozin.

Hot-Melt 3D Extrusion for the Fabrication of Customizable Modified-Release Solid Dosage Forms.

In this work, modified-release solid dosage forms were fabricated by adjusting geometrical properties of solid dosage forms through hot-melt 3D extrusion (3D HME). Using a 3D printer with air pressure driving HME system, solid dosage forms containing ibuprofen (IBF), polyvinyl pyrrolidone (PVP), and polyethylene glycol (PEG) were printed by simultaneous HME and 3D deposition. Printed solid dosage forms were evaluated for their physicochemical properties, dissolution rates, and floatable behavior.

Physicochemical properties and drug-release mechanisms of dual-release bilayer tablet containing mirabegron and fesoterodine fumarate.

In this study, a dual release bi-layer tablet containing Fesoterodine fumarate (Fst) 5 mg and Mirabegron (Mrb) 50 mg was prepared to investigate the different release behavior of each drug in bilayer tablet. The bilayer tablet was prepared based on monolayer-tablet formulation of each drug. The optimized bi-layer tablet showed an in vitro dissolution profile similar to commercial reference tablets Toviaz and Betmiga, based on a satisfactory similarity factor.

Preparation, Characterization, and Stability Evaluation of Taste-Masking Lacosamide Microparticles.

Lacosamide (LCM) is a third-generation antiepileptic drug. Selective action of the drug on voltage-gated sodium channels reduces side effects. Oral administration of LCM shows good pharmacokinetic profile.

Formulation and evaluation of carrier-free dry powder inhaler containing sildenafil.

Pulmonary delivery of sildenafil for the treatment of pulmonary arterial hypertension could overcome the limitations of intravenous and oral administration routes, such as poor patient compliance and systemic side effects. In this study, a carrier-free dry powder inhaler (DPI) formulation was developed, using spray drying technique and L-leucine as a dispersibility enhancer. Sildenafil citrate salt and sildenafil free base were evaluated for drug transport using a Calu-3 cell model, and their suitability for DPI production by spray drying was tested.

The role of lactose carrier on the powder behavior and aerodynamic performance of bosentan microparticles for dry powder inhalation.

In this study, we prepared carrier-based formulations for dry powder inhalers by mixing bosentan microparticles with carrier, prepared in three separate types of lactose. Spray-dried, milled and sieved lactose resulted in formulations with various shapes, surface morphology and particle size distributions. In the spray-dried lactose, the micronized bosentan particles were trapped and strongly interlocked in the rugged surface of spray-dried lactose, whereas in the milled and sieved lactose they exhibited lower binding affinity onto the smooth surface of carrier.

Application of continuous twin screw granulation for the metformin hydrochloride extended release formulation.

This study focuses on evaluating the potential of transferring from a batch process to continuous process for manufacturing of the extended release formulation. Metformin hydrochloride (HCl) was used in the model formulation which was intended to contain the high amount of hydrophilic drug. The effects of barrel temperature, binder type, powder feed rate, and screw speed on granule properties (size and strength) and torque value in twin screw granulation were investigated.

Formulation and in vitro/in vivo evaluation of chitosan-based film forming gel containing ketoprofen.

The film forming gel, adhered to skin surfaces upon application and formed a film, has an advantage onto skin to provide protection and continuous drug release to the application site. This study aimed to prepare a chitosan-based film forming gel containing ketoprofen (CbFG) and to evaluate the CbFG and film from CbFG (CbFG-film). CbFG were prepared with chitosan, lactic acid and various skin permeation enhancers.

Implementation of Quality by Design for Formulation of Rebamipide Gastro-retentive Tablet.

The purpose of the present study was to develop a rebamipide (RBM) gastro-retentive (GR) tablet by implementing quality by design (QbD). RBM GR tablets were prepared using a sublimation method. Quality target product profile (QTPP) and critical quality attributes (CQAs) of the RBM GR tablets were defined according to the preliminary studies.

Release kinetics of highly porous floating tablets containing cilostazol.

This study focuses on developing a highly porous floating tablet containing cilostazol. The underlying release mechanism of cilostazol from porous and floating tablets in dissolution media containing surfactants was investigated. The tablets were prepared by compressing granules and excipients with a sublimating agent, followed by sublimation under vacuum.

Preparation and physicochemical characterization of spray-dried and jet-milled microparticles containing bosentan hydrate for dry powder inhalation aerosols.

The objectives of this study were to prepare bosentan hydrate (BST) microparticles as dry powder inhalations (DPIs) via spray drying and jet milling under various parameters, to comprehensively characterize the physicochemical properties of the BST hydrate microparticles, and to evaluate the aerosol dispersion performance and dissolution behavior as DPIs. The BST microparticles were successfully prepared for DPIs by spray drying from feeding solution concentrations of 1%, 3%, and 5% (w/v) and by jet milling at grinding pressures of 2, 3, and 4 MPa. The physicochemical properties of the spray-dried (SD) and jet-milled (JM) microparticles were determined via scanning electron microscopy, atomic force microscopy, dynamic light scattering particle size analysis, Karl Fischer titration, surface analysis, pycnometry, differential scanning calorimetry, powder X-ray diffraction, and Fourier transform infrared spectroscopy.

Formulation and in Vitro Evaluation of Self-microemulsifying Drug Delivery System Containing Fixed-Dose Combination of Atorvastatin and Ezetimibe.

This paper focuses on the development and physicochemical characterization of a self-microemulsifying drug delivery system (SMEDDS) containing a fixed-dose combination of atorvastatin (ATR) and ezetimibe (EZT). The solubility of both drugs was determined in excipient screening studies. Ternary-phase diagrams were drawn for 27 systems composed of different surfactants, cosurfactants, and oils at different surfactant-to-cosurfactant (S/CoS) ratios, and the system exhibiting the largest percentage area of the self-microemulsifying region was selected.

Design and in vivo evaluation of oxycodone once-a-day controlled-release tablets.

The aim of present study was to design oxycodone once-a-day controlled-release (CR) tablets and to perform in vitro/in vivo characterizations. Release profiles to achieve desired plasma concentration versus time curves were established by using simulation software and reported pharmacokinetic parameters of the drug. Hydroxypropyl methylcellulose (HPMC) 100,000 mPa·s was used as a release modifier because the polymer was found to be resistant to changes in conditions of the release study, including rotation speed of paddle and ion strength.

Preparation of sildenafil citrate microcapsules and in vitro/in vivo evaluation of taste masking efficiency.

The aim of the present study was to prepare the particulate taste-masking system to mask the bitter taste of sildenafil citrate (SC), a well-known phosphodiesterase-5 inhibitor used for erectile dysfunction (ED) and pulmonary artery hypertension (PAH). It was evaluated for the taste masking efficiency by the in vitro measurement using electronic tongue (e-tongue) system and the in vivo human panel sensory test. Microcapsules were prepared by microencapsulation with a gastro-soluble polymer, Eudragit(®) E100 (E100), using a spray drying technique at four different weight ratios (2:1, 1:1, 1:2, and 1:3).

Organic-aqueous crossover coating process for the desmopressin orally disintegrating microparticles.

The purpose of the present study was to prepare desmopressin orally disintegrating microparticles (ODMs) using organic-aqueous crossover coating process which featured an organic sub-coating followed by an aqueous active coating. Sucrose beads and hydroxypropyl cellulose (HPC) were used as inert cores and a coating material, respectively. Characterizations including size distribution analysis, in-vitro release studies and in-vitro disintegration studies were performed.

Preparation and evaluation of dual-mode floating gastroretentive tablets containing itraconazole.

The aims of the present study were to prepare new dual-mode floating gastroretentive tablets (DF-GRT) containing itraconazole (ITR) and to evaluate influence of the dosage forms on pharmacokinetic parameters of ITR. The solubility of ITR was enhanced around 200 times (from 1.54 to 248.

Formulation and in vivo human bioavailability of dissolving tablets containing a self-nanoemulsifying itraconazole solid dispersion without precipitation in simulated gastrointestinal fluid.

To investigate the performance of a solid-state self-nanoemulsifying system with no precipitation in gastric and intestinal fluid, itraconazole (ITZ) was selected as a model drug because of its practically insoluble nature in intestinal fluid. A self-nanoemulsifying ITZ solid dispersion (SNESD) system was prepared as follows: (1) establishment of self-nanoemulsifying composition via the hot melting method, (2) solidification with fumed silicon dioxide (Aerosil 300) via adsorption to prepare SNESD and (3) preparation of a directly compressible tablet containing SNESD. This SNESD was easily formulated in the form of a dissolving tablet and provided a favourable nanoemulsifying microenvironment with no precipitation in the testing media.

Physical properties and in vivo bioavailability in human volunteers of isradipine using controlled release matrix tablet containing self-emulsifying solid dispersion.

Poorly water-soluble drug with a short half-life such as isradipine (IDP) offer challenges in the controlled release formulation because of low dissolution rate and poor bioavailability. Self-emulsifying solid dispersions (SESD) of IDP consisted of surfactant and fatty acid in poloxamer 407 (POX 407) as a carrier and were manufactured by the melting method. Then, controlled release HPMC matrix tablet containing SESD were prepared via direct compression.

Formulation and biopharmaceutical evaluation of a transdermal patch containing aceclofenac.

To reduce the adverse effects of aceclofenac that accompanied with oral administration of this drug, transdermal patches in the form of drug-in-adhesive (DIA) patches, containing aceclofenac, were formulated. The effect of formulation factors on the skin permeation of the drug and physical properties of the patch were evaluated using excised rat skins. The optimized patch contained 12 % aceclofenac and 20 % lauryl alcohol in DT-2852 as a pressure-sensitive adhesive.

Preparation and evaluation of sustained-release doxazosin mesylate pellets.

Doxazosin mesylate (DXM) sustained release pellets were prepared by an extrusion-spheronization and fluid-bed coating technique. The core pellets containing DXM were prepared by extrusion-spheronization technique, and coated by a fluid-bed coater to control the release of DXM. The factors affecting to properties of pellets, such as diluent content, type and coating level of coating agents and plasticizers were studied in the present study.

Preparation of highly porous gastroretentive metformin tablets using a sublimation method.

The present investigation is aimed to formulate floating gastroretentive tablets containing metformin using a sublimation material. In this study, the release of the drug from a matrix tablet was highly dependent on the polymer concentrations. In all formulations, initial rapid drug release was observed, possibly due to the properties of the drug and polymer.