Design of Nanocrystalline Suspension of Dutasteride for Intramuscular Prolonged Delivery.

The aim of the study is to formulate an injectable nanocrystalline suspension (NS) of dutasteride (DTS), a hydrophobic 5α-reductase inhibitor used to treat benign prostatic hyperplasia and scalp hair loss, for parenteral long-acting delivery. A DTS-loaded NS (DTS-NS, 40 mg/mL DTS) was prepared using a lab-scale bead-milling technique. The optimized DTS-NS prepared using Tween 80 (0.

Tricaprylin-based drug crystalline suspension for intramuscular long-acting delivery of entecavir with alleviated local inflammation.

In order to ensure prolonged pharmacokinetic profile along with local tolerability at the injection site, tricaprylin-based drug crystalline suspension (TS) was designed and its local distribution, pharmacokinetics, and inflammatory response, were evaluated with conventional aqueous suspension (AS). As model drug particles, entecavir 3-palmitate (EV-P), an ester lipidic prodrug for entecavir (EV), was employed. The EV-P-loaded TS was prepared by ultra-sonication method.

Carboxymethyl cellulose-based rotigotine nanocrystals-loaded hydrogel for increased transdermal delivery with alleviated skin irritation.

Transdermal rotigotine (RTG) therapy is prescribed to manage Parkinson's disease (Neupro® patch). However, its use is suffered from application site reactions. Herein, drug nanocrystalline suspension (NS)-loaded hydrogel (NS-HG) employing polysaccharides simultaneously as suspending agent and hydrogel matrix was constructed for transdermal delivery, with alleviated skin irritation.

Design of High-Payload Ascorbyl Palmitate Nanosuspensions for Enhanced Skin Delivery.

A high-payload ascorbyl palmitate (AP) nanosuspension (NS) was designed to improve skin delivery following topical application. The AP-loaded NS systems were prepared using the bead-milling technique, and softly thickened into NS-loaded gel (NS-G) using hydrophilic polymers. The optimized NS-G system consisted of up to 75 mg/mL of AP, 0.

Novel bioequivalent oral disintegrating tablet of aripiprazole prepared by direct compression technique with shortened disintegration time.

Herein, we aimed to formulate a novel oral disintegrating tablet (ODT) of aripiprazole (ARP) capable of rapid disintegration using a direct compression technique. Different ODTs were fabricated with directly compressible excipients, and their disintegration time, wettability (water absorption ratio and wetting time), and mechanical properties (hardness and friability) were evaluated. The optimized ODT comprised F-Melt® type C, Prosolv® SMCC HD90, and Na croscarmellose (10 mg of ARP in a 130 mg tablet).

Novel Bioequivalent Tablet of Solifenacin Succinate Prepared Using Direct Compression Technique for Improved Chemical Stability.

We designed a bioequivalent tablet form of solifenacin succinate (SOL) with an improved storage stability using a direct compression (DC) technique. An optimal direct compressed tablet (DCT) containing an active substance (10 mg), lactose monohydrate, and silicified microcrystalline cellulose as diluents, crospovidone as a disintegrant, and hydrophilic fumed silica as an anti-coning agent was constructed by evaluating the drug content uniformity, mechanical properties, and in vitro dissolution. The physicochemical and mechanical properties of the DCT were as follows: drug content 100.

Neutral Oil-Incorporated Liposomal Nanocarrier for Increased Skin Delivery of Ascorbic Acid.

In this study, a neutral oil-incorporated liposomal system (lipo-oil-some, LOS) was designed to improve the skin absorption of ascorbic acid (Vit C), and the effects of an edge activator and neutral oil on the skin absorption of Vit C were evaluated. As components of the LOS system, sodium deoxycholate, polysorbate 80, and cholesterol were screened as edge activators, and camellia oil, tricaprylin, and grapeseed oil were employed as neutral oils. The LOS systems prepared by the ethanol injection method were spherical in shape, 130-350 nm in size, and had 4-27% Vit C loading efficiency (%).

Design of Novel Tricaprylin-Incorporated Multi-Layered Liposomal System for Skin Delivery of Ascorbic Acid with Improved Chemical Stability.

L-ascorbic acid (Vit C) possesses a variety of dermatological functions in maintaining skin health and anti-aging properties. However, its topical application is challenging owing to its liability to light, oxygen, or heat. Therefore, in this study, a novel liposomal system, including a lipophilic neutral oil named a lipo-oil-some (LOS), was designed to improve the chemical stability and aid the skin absorption of Vit C.

Effect of Dispersion Medium on Pharmacokinetic Profile of Rotigotine Crystalline Suspension following Subcutaneous Injection.

Rotigotine (RTG) is prescribed as a once-daily transdermal patch for managing early Parkinson’s disease (PD), which presents issues such as skin irritation and poor patient adherence. Therefore, the aims of the present study were to formulate aqueous and oily vehicle-based RTG crystalline suspensions for prolonged delivery and to compare their pharmacokinetic profiles and the local behaviors of RTG crystals. RTG-loaded aqueous (AS) and oil suspensions (OS) were fabricated using bead-milling technology (100 mg/mL as RTG), employing carboxymethyl cellulose and sesame oil as suspending agent and oily vehicle, respectively.

Design of Montelukast Nanocrystalline Suspension for Parenteral Prolonged Delivery.

Background: Montelukast (MTK), a representative leukotriene receptor antagonist, is currently being investigated as a potential candidate for treating Alzheimer's disease. For potent and effective dosing in elderly patients, a parenteral prolonged delivery system is favored, with improved medication adherence with reduced dosage frequency.

Purpose: This study aimed to design a nanocrystalline suspension (NS)-based MTK prolonged delivery system and evaluate its pharmacokinetics profile and local tolerability following subcutaneous administration.

Effect of particle size on in vivo performances of long-acting injectable drug suspension.

Herein, entecavir-3-palmitate (EV-P), an ester prodrug of entecavir (EV), was employed as a model drug, and the effect of drug particle size on in vivo pharmacokinetic profiles and local inflammatory responses, and those associations were evaluated following intramuscular (IM) injection. EV-P crystals with different median diameters (0.8, 2.

Montelukast microsuspension with hypromellose for improved stability and oral absorption.

Oral montelukast (MTK) is prescribed to treat asthma or rhinitis, and is clinically investigated as new medication in the treatment of Alzheimer's dementia. Herein, in order to better patient's compliance, microsuspensions (MSs)-based oral liquid preparations of montelukast (MTK) were formulated with polymeric suspending agents including hypromellose (HPMC), and those drug-polymer interaction, physicochemical stability, dissolution, and in vivo pharmacokinetic profile was evaluated. When amorphous MTK particle was suspended in aqueous vehicle, it was readily converted into crystalline form and grown into aggregates, drastically lowering dissolution rate.

Effect of Penetration Enhancers on Toenail Delivery of Efinaconazole from Hydroalcoholic Preparations.

The incorporation of permeation enhancers in topical preparations has been recognized as a simple and valuable approach to improve the penetration of antifungal agents into toenails. In this study, to improve the toenail delivery of efinaconazole (EFN), a triazole derivative for onychomycosis treatment, topical solutions containing different penetration enhancers were designed, and the permeation profiles were evaluated using bovine hoof models. In an in vitro permeation study in a Franz diffusion cell, hydroalcoholic solutions (HSs) containing lipophilic enhancers, particularly prepared with propylene glycol dicaprylocaprate (Labrafac PG), had 41% higher penetration than the HS base.

Montelukast Nanocrystals for Transdermal Delivery with Improved Chemical Stability.

A novel nanocrystal system of montelukast (MTK) was designed to improve the transdermal delivery, while ensuring chemical stability of the labile compound. MTK nanocrystal suspension was fabricated using acid-base neutralization and ultra-sonication technique and was characterized as follows: approximately 100 nm in size, globular shape, and amorphous state. The embedding of MTK nanocrystals into xanthan gum-based hydrogel caused little changes in the size, shape, and crystalline state of the nanocrystal.

Quantitative assessment of steroid amount in the tissue after epidural steroid injection: a new rabbit model.

Background: To develop a rabbit epidural steroid injection (ESI) model for analyzing steroid retention in the tissue, and to assess the difference in steroid retention in the model according to the location and time elapsed after ESI.

Methods: Fluoroscopy-guided ESI was performed using the interlaminar approach between the lowest two lumbar segments in 13 female New Zealand white rabbits. Four rabbits were allocated to each of three different groups according to the time of sacrifice: 3, 7, and 15 days post-ESI; the remaining rabbit was sacrificed immediately post-ESI to obtain baseline data.

Design and In Vivo Pharmacokinetic Evaluation of Triamcinolone Acetonide Microcrystals-Loaded PLGA Microsphere for Increased Drug Retention in Knees after Intra-Articular Injection.

A novel polymeric microsphere (MS) containing micronized triamcinolone acetonide (TA) in a crystalline state was structured to provide extended drug retention in joints after intra-articular (IA) injection. Microcrystals with a median diameter of 1.7 μm were prepared by ultra-sonication method, and incorporated into poly(lactic--glycolic acid)/poly(lactic acid) (PLGA/PLA) MSs using spray-drying technique.

Pharmacokinetics and four-week repeated-dose toxicity of hyaluronic acid and ketorolac combination following intra-articular administration in normal rats.

Intra-articular (IA) injection of hyaluronic acid (HA) in combination with nonsteroidal anti-inflammatory drugs, such as ketorolac (KL), have been clinically investigated to provide more rapid and profound pain relief in patients with osteoarthritis. However, its safety, local tolerance, and potential for pharmacokinetic interaction have not been assessed. In this study, the pharmacokinetics and toxicity of a combination of HA and KL were evaluated in normal rats following four-week repeated-dose injection.

Design and in vivo evaluation of entecavir-3-palmitate microcrystals for subcutaneous sustained delivery.

The objectives of this study were to formulate microcrystals of entecavir-3-palmiate (EV-P), a palmitic acid ester of entecavir (EV), and evaluate the influence of particle size on its pharmacokinetic behavior following subcutaneous (SC) injection. Systemic toxicity and local tolerability of the hepatitis B anti-viral suspension were further evaluated in normal rats. EV-P microcrystals possessing median diameters of 2.

Novel Extended-Release Multiple-Unit System of Imidafenacin Prepared by Fluid-Bed Coating Technique.

The objective of this study was to formulate once-a-day extended-release (ER) pellet system of imidafenacin (IDN), a recently approved urinary antispasmodic agent with twice-a-day dosing regimen. The sugar sphere pellets were firstly layered with IDN and hypromellose and then coated with Eudragit RS (copolymers of acrylic and methacrylic acid esters), employed as a release modifier, using a fluid-bed coater. Solid-state characterizations using solid-state X-ray diffraction and differential scanning calorimeter indicated that the antispasmodic agent was homogeneously layered onto the pellets in an amorphous state.

Microsuspension of fatty acid esters of entecavir for parenteral sustained delivery.

Entecavir (EV), an anti-viral agent for hepatitis B infection, should be administered under fasted state, as intestinal absorption of this hydrophilic compound is markedly decreased under post-prandial conditions. Herein, in order to improve therapeutic adherence, a parenteral sustained delivery system was constructed, by synthesizing water-insoluble ester prodrugs of the nucleotide analogous with fatty acids. EV-3-palmitate (named EV-P), exhibited the lowest solubility in phosphate buffered saline (pH 7.

Synthesis and Physicochemical Evaluation of Entecavir-Fatty Acid Conjugates in Reducing Food Effect on Intestinal Absorption.

The oral bioavailability of entecavir (EV), an anti-viral agent commonly prescribed to treat hepatitis B infections, is drastically reduced under a post-prandial state. This is primarily due to its low permeability in the gastrointestinal tract. To reduce the food effect on the intestinal absorption of the nucleotide analogue, four lipidic prodrugs were synthesized via the esterification of the primary alcohol of EV with fatty acids (hexanoic acid, octanoic acid, decanoic acid, and dodecanoic acid).

Formulation and in vivo pharmacokinetic evaluation of ethyl cellulose-coated sustained release multiple-unit system of tacrolimus.

A novel once-a-day sustained-release (SR) system of tacrolimus (FK506), a poorly water-soluble immunosuppressive agent, was designed employing ethyl cellulose (EC) polymer as release retardant. Drug (5 mg) was layered onto sugar spheres (518.3 mg) with hypromellose (5 mg), to transform the drug from a crystalline to an amorphous form.

A Polyvinylpyrrolidone-Based Supersaturable Self-Emulsifying Drug Delivery System for Enhanced Dissolution of Cyclosporine A.

A novel supersaturable self-emulsifying drug delivery system (S-SEDDS) of cyclosporine A (CyA)-a poorly water-soluble immunosuppressant-was constructed in order to attain an apparent concentration⁻time profile comparable to that of conventional SEDDS with reduced use of oil, surfactant, and cosolvent. Several hydrophilic polymers, including polyvinylpyrrolidone (PVP), were employed as precipitation inhibitors in the conventional SEDDS, which consists of corn oil-mono-di-triglycerides, polyoxyl 40 hydrogenated castor oil, ethanol, and propylene glycol. PVP-incorporated pre-concentrate (CyA:vehicle ingredients:PVP = 1:4.

Increased localized delivery of piroxicam by cationic nanoparticles after intra-articular injection.

Piroxicam (PRX), a potent nonsteroidal anti-inflammatory drug, is prescribed to relieve postoperative and/or chronic joint pain. However, its oral administration often results in serious gastrointestinal adverse effects including duodenal ulceration. Thus, a novel cationic nanoparticle (NP) was explored to minimize the systemic exposure and increase the retention time of PRX in the joint after intra-articular (IA) injection, by forming micrometer-sized electrostatic clusters with endogenous hyaluronic acid (HA) in the synovial cavity.

Determination of piroxicam from rat articular tissue and plasma based on LC-MS/MS.

Osteoarthritis (OA) is the most common type of arthritis. To manage OA, in general, oral administration of non-steroidal anti-inflammatory drugs (NSAIDs) is used. Recently, the analgesic and anti-inflammatory efficacy of piroxicam (PX), a long-acting NSAID, by intra-articular (IA) administration in OA was reported, and the possibility that PX is distributed in articular tissues at a certain concentration was raised.