Comparison of the relative stability of pharmaceutical cocrystals consisting of paracetamol and dicarboxylic acids.

Objective: The aim of this study is to evaluate the relative stability of pharmaceutical cocrystals consisting of paracetamol (APAP) and oxalic acid (OXA) or maleic acid (MLA).

Significance: These observations of cocrystal stability under various conditions are useful coformer criteria when cocrystals are selected as the active pharmaceutical ingredient in drug development.

Method: The relative stability was determined from the preferentially formed cocrystals under various conditions.

Enhanced dissolution and skin permeation profiles of epalrestat with β-cyclodextrin derivatives using a cogrinding method.

Epalrestat (EPL) is a water-insoluble drug (14μM) that inhibits aldose reductase. This study investigated the interactions between β-cyclodextrin (CD) derivatives and EPL to determine the solubilizing effect on EPL from phase solubility diagrams. We improved the solubility of EPL in water by adding β-CD derivatives.

Involvement of a proton-coupled organic cation antiporter in the blood-brain barrier transport of amantadine.

The blood-to-brain transport of amantadine, a weak N-methyl-d-aspartate (NMDA) antagonist, has been shown previously to participate in the cationic drug-sensitive transport system across the mouse blood-brain barrier (BBB). The purpose of the present study was to characterize the influx transport system by means of both an in situ mouse brain perfusion technique and in vitro studies using rat immortalized brain capillary endothelial cells (GPNT). The observed concentration-dependent initial uptake rate of [(3) H]amantadine suggested the involvement of a carrier-mediated transport mechanism.

Studies on uniformity of the active ingredients in acetaminophen suppositories re-solidified after melting under high temperature conditions.

The target of the present pharmaceutical study was the antipyretic analgesic, acetaminophen; its suppository form is usually split when used in pediatric patients. We focused on the active ingredient uniformity in these products, which were re-solidified after melting under high temperature condition. When sections of the cut surfaces of the seven acetaminophen suppository products (SUP-A-G) commercially available in Japan were visualized by polarized microscopy, acetaminophen crystals that were dispersed in the base were identified.

Possible involvement of cationic-drug sensitive transport systems in the blood-to-brain influx and brain-to-blood efflux of amantadine across the blood-brain barrier.

The purpose of this study was to characterize the brain-to-blood efflux transport of amantadine across the blood-brain barrier (BBB). The apparent in vivo efflux rate constant for [(3) H]amantadine from the rat brain (keff ) was found to be 1.53 × 10(-2) min(-1) after intracerebral microinjection using the brain efflux index method.

Novel pharmaceutical cocrystal consisting of paracetamol and trimethylglycine, a new promising cocrystal former.

Paracetamol (APAP), a frequently used antipyretic drug, has poor compression moldability. In this study, we identified a novel cocrystal consisting of APAP and trimethylglycine (TMG) that exhibits improved tabletability. TMG was used instead of oxalic acid (OXA), which is a coformer reported previously.

Comparative pharmaceutical evaluation of brand and generic clobetasone butyrate ointments.

In the present study, we performed comprehensive pharmaceutical evaluation among an original clobetasone butyrate (CLB) ointment product and three generic products. Although spherocrystal images were observed under a polarizing microscope for only Kindavate®, the original product, distribution of active and inactive ingredients was chemically equivalent between the original and generic medicine by the attenuated total reflection infrared spectroscopy. These results suggest that the spherocrystals observed in Kindavate® are composed of hydrocarbon.

Effect of terpenes on the skin permeation of lomerizine dihydrochloride.

Purpose: Lomerizine dihydrochloride (LOM) is a Ca2+ channel blocker used as an antimigraine drug, which is currently administered orally in Japan. We therefore investigated the effect of terpenes in propylene glycol (PG) solvent on the percutaneous absorption of LOM by hairless mouse skin.

Methods: Attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), confocal laser scanning microscopy (CLSM), and small angle X-ray scattering (SAXS) were carried out to analyze the effects of terpene enhancers on the biophysical properties of the stratum corneum (SC) of the skin.

Blood-brain barrier transport of an essential amino acid after cerebral ischemia reperfusion injury.

Under pathophysiological conditions such as -cerebral ischemia-reperfusion (IR), damage to cerebrovascular endothelial cells causes alterations in the blood-brain barrier (BBB) function that can exacerbate neuronal cell injury and death. Clarifying changes in BBB transport in the early period of IR is important for understanding BBB function during therapy after cerebral ischemia. The present study was aimed at clarifying changes during IR in the BBB transport of L-phenylalanine (Phe) as a substrate of L-type amino acid transporter 1.

[Factors contributing to increases in serum creatinine following treatment with a sulfamethoxazole-trimethoprim combination product: retrospective analysis of Japanese patients with normal renal function].

  Japanese patients with normal renal function were retrospectively analyzed to characterize increases in serum creatinine (SCr) observed following the use of a sulfamethoxazole-trimethoprim (SMX-TMP) combination product and identify factors affecting these increases. In the patients studied (n=49), an individual comparison was conducted for the three factors of age group [≤74 years (n=21) vs. ≥75 years (n=28)], sex [male (n=24) vs.

Effects of slow-releasing colistin microspheres on endotoxin-induced sepsis.

Lipopolysaccharide (LPS) is a major contributing factor to endotoxic shock. Colistin specifically binds to LPS. However, it has the disadvantages that adverse reactions are common and it has a short half-life.

Evaluation of the degree of mixing of combinations of dry syrup, powder, and fine granule products in consideration of particle size distribution using near infrared spectrometry.

We used near infrared (NIR) spectroscopy to evaluate the degree of mixing of blended dry syrup (DS) products whose particle sizes are not specified in the Revised 16th Edition of the Japanese Pharmacopoeia, and also evaluated the degree of mixing when powder products or fine granule products were added to DS products. The data obtained were used to investigate the relationship between the particle size distributions of the products studied and the degree of mixing. We found that the particle size distribution characteristics of the 15 DS products studied can be broadly classified into 5 types.

Pharmaceutical evaluation of steroidal ointments by ATR-IR chemical imaging: distribution of active and inactive pharmaceutical ingredients.

We recently used micro attenuated total reflection infrared (ATR-IR) spectroscopy to conduct imaging analysis of ointments and evaluate the distributions of the active pharmaceutical ingredient (API) and excipients. An alclometasone dipropionate (ALC) ointment was used as a model product. Almeta, a brand-name product, had a domain with absorbance at 1656 cm(-1) attributable to the carbonyl group of ALC, the API.

Stabilization of a supersaturated solution of mefenamic acid from a solid dispersion with EUDRAGIT(®) EPO.

Purpose: The stabilization mechanism of a supersaturated solution of mefenamic acid (MFA) from a solid dispersion with EUDRAGIT(®) EPO (EPO) was investigated.

Methods: The solid dispersions were prepared by cryogenic grinding method. Powder X-ray diffractometry, in vitro dissolution test, in vivo oral absorption study, infrared spectroscopy, and solid- and solution-state NMR spectroscopies were used to characterize the solid dispersions.

Effect of particle size on skin permeation and retention of piroxicam in aqueous suspension.

The effects of particle size on the skin permeation and retention of piroxicam (PXC) in an aqueous suspension were investigated. PXC particles of about 23 nm, 173 nm, and 2.1 microm in size were prepared by the cogrinding of PXC/polyvinylpyrrolidone (PVP) K12/sodium dodecyl sulfate physical mixture (mean particle size, 9.

[Adhesion loss of syrups in a metering glass which consists of a low surface free energy material].

We previously reported a strong positive correlation between syrup viscosity and the rate of syrup loss due to adhesion to a glass metering device. In this study, we examined differences in the surface free energies of metering devices made of different polymeric materials, since reducing adhesion loss to metering devices could improve the efficiency of drug preparation involving highly viscous syrups. Among metering devices made of glass only, glass with a silicone coating (SLC), polypropylene (PP), and polymethylpentene (PMP) the surface free energy of the glass-only metering device was the highest (49.

Effect of beta-cyclodextrin on the degradation rate of amoxicillin in acidic solution.

The formation of an inclusion complex of amoxicillin (AMX) with beta-cyclodextrin (beta-CD) in aqueous solution was confirmed by a solubility method and proton nuclear magnetic resonance (1H-NMR) spectroscopy. The apparent stability constant for the inclusion complex was 10.72 M(-1) in water at 25 degrees C.

Involvement of an influx transporter in the blood-brain barrier transport of naloxone.

Naloxone, a potent and specific opioid antagonist, has been shown in previous studies to have an influx clearance across the rat blood-brain barrier (BBB) two times greater than the efflux clearance. The purpose of the present study was to characterize the influx transport of naloxone across the rat BBB using the brain uptake index (BUI) method. The initial uptake rate of [(3)H]naloxone exhibited saturability in a concentration-dependent manner (concentration range 0.

Synergistic effect of isopropyl myristate and glyceryl monocaprylate on the skin permeation of pentazocine.

The aim of this investigation was to assess the applicability of lipid bilayer alteration using a combination of isopropyl myristate (IPM) and glyceryl monocaprylate (GEFA-C(8)) to the enhancement of pentazocine (PTZ) permeation through hairless mouse skin. The skin permeability of PTZ was enhanced by increasing the concentration of GEFA-C(8) up to 10% w/w in combination with IPM. Attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) and small angle X-ray diffraction (SAXD) were carried out to analyze the effects of these enhancers on the biophysical properties of the stratum corneum (SC) of the skin, and on the permeation of PTZ.

Ascorbyl dipalmitate/PEG-lipid nanoparticles as a novel carrier for hydrophobic drugs.

L-ascorbyl 2,6-dipalmitate (ASC-DP), a fatty ester derivative of ascorbic acid, is poorly soluble in water and does not spontaneously form micelles or liposomal structures in water. In this study, we attempted to prepare an ASC-DP/surfactant nano-sized complex as a carrier for hydrophobic drugs. Samples were prepared by hydrating a solvent-evaporated film of ASC-DP/surfactant at a molar ratio of 1:1.

Homogeneous nanoparticles to enhance the efficiency of a hydrophobic drug, antihyperlipidemic probucol, characterized by solid-state NMR.

A low absorption in the gastrointestinal tract of hydrophobic pharmaceutical compounds in use today considerably limits their bioavailability, and therefore they are taken in large doses in order to reach the therapeutic plasma concentration, which inevitably results in undesired side effects. In this study, we demonstrate a new nanoparticle approach to overcome this problem, and our experimental results show that this approach has a high efficiency of drug loading and is easily adaptable to industrial scale. Characterization of nanoparticles containing a cholesterol-lowering hydrophobic drug, probucol, using a variety of biophysical techniques revealed higher homogeneity of these particles compared to those prepared using other approaches.

Blood-brain barrier transport of naloxone does not involve P-glycoprotein-mediated efflux.

The blood-brain barrier (BBB) transport of naloxone, a potent and specific opioid antagonist, was investigated in rats using the brain uptake index method and the brain efflux index method. The apparent influx clearance of [(3)H]naloxone across the BBB was 0.305 mL/min/g brain.

Characterization of multicomponent crystal formed between indomethacin and lidocaine.

Purpose: Crystalline complex was formed between indomethacin (IDM) and lidocaine (LDC) at molar ratio 2:1 from ethanol solution. The purpose of this study was elucidation of an interactive manner between IDM and LDC in ethanol solution and mechanism of the complex formation through solid state as well as liquid state.

Methods: The chemical and physical nature of the complex was clearly elucidated by the alliance of powder X-ray diffractometry, differential scanning calorimetry, and infrared spectroscopy.

Nanoparticle processing in the solid state dramatically increases the cell membrane permeation of a cholesterol-lowering drug, probucol.

High cholesterol levels (or hypercholesterolemia) are linked with many diseases, particularly with the risk of coronary heart diseases. Probucol is commonly used to reduce cholesterol in blood. While the effectiveness of this drug highly depends on its solubility, unfortunately, it is nearly insoluble (solubility is 5 ng/mL in water).