Pharmaceutical Additives Research Articles

AS ATIVIDADES ANTIOXIDANTES DA PERESKIA ACULEATA MILLER

Ora-pro-nóbis (Pereskia aculeata Miller), a plant native to Brazil, is valued in traditional medicine for its nutritional and therapeutic properties. Recently, scientific interest has grown, particularly due to its antioxidant activities. It is rich in vitamins, iron, and proteins and has shown therapeutic effects such as wound healing and treatment of gastrointestinal diseases. Identified bioactive compounds include phenolic acids, like caffeic acid, and flavonoids, such as quercetin and kaempferol. Studies demonstrate high antioxidant and antimicrobial activity, with effectiveness in inhibiting both Gram-positive and Gram-negative bacteria. The plant's mucilage, known for its water retention capacity, is valuable in the food industry as a thickening and stabilizing agent and also has wound-healing properties, leading to its use in ointments. The biopolymers found, such as arabinogalactans, have potential applications in food and pharmaceutical additives. Ora-pro-nóbis is a rich source of bioactive compounds with potential for new nutraceutical and pharmaceutical products, promoting health and disease prevention.

Thermodynamic studies on the formation of ion-pair cobalt complexes in acetone–water mixtures

Dicarboxylic acids are stronoger acids than moncraboxylic acids and more soluble in water due to the presence of two carboxylic (–COOH) groups which are industrially important in producing polyester, polyamides, and polyols and as a pioneer to pharmaceutical additives. Succinic acid is one of the most prosperous chemicals that can be generated from renewable resources which can be used in the industries of antiseptics, cosmetics, sutures, drugs, solvents, detergents, herbicides, fungicides, synthetic resins, and inks. The ion–pair formation is very important in diferent applications, used widely for inorganic analysis by liquid chromatography and used for the heavy metal removal from waste water, so studing the ion-pair association constant (KA) formed between chloropentamminecobalt(III) cation [CpX2+] and a different ligands of dicarboxylate anions (AC2-), have been determined by EMF technique in different compositions of acetone aqueous media (0–44.20 wt% acetone) for succinic acid and for the other dicarboxylic acids (Maleic, Malonic and Malic) in the same solvent composition (40 wt% acetone) with in temperature range (30 – 60 °C). The thermodynamic association properties (ΔGA°, ΔHA° and ΔSA°) have been estimated and discussed. Extra thermodynamic correlations like ΔHA°- ΔSA° and ΔGA°- ΔGI(orII)° (where I and II are mentioned for the first and second dissociation constant of the dicarboxylic acids) in different compositions of acetone aqueous media for succinic acid and in fixed solvent composition for the other dicarboxylic acids were examined in order to give more information about the behavior of solvent molecules and its effect on formation of the ion-pair molecules. In addition, The Gibbs free energy of transfer for the association process ΔGA°(t) from water to acetone mixed solvents were calculated for succinic acid in order to indicate the spontaneous nature and the stabilization of the ion-pair by increasing the acetone weight percent in the mixed acetone – aqueous media. The linear correlation between pKD values and the relative permittivity of acetone aqueous medium is in accordance to Born’s equation.

The Development and Characterization of Novel Ionic Liquids Based on Mono- and Dicarboxylates with Meglumine for Drug Solubilizers and Skin Permeation Enhancers.

In this study, we synthesized a family of novel ionic liquids (ILs) with meglumine (MGM) as cations and tartaric acid (TA), azelaic acid (AA), geranic acid (GA), and capric acid (CPA) as anions, using pharmaceutical additives via simple acid-base neutralization reactions. The successful synthesis was validated by attenuated total reflection-Fourier transform infrared (ATR-FTIR) and powder X-ray diffraction (PXRD). Thermal analysis using differential scanning calorimetry confirmed the glass transition temperature of MGM-ILs to be within the range of -43.4 °C--13.8 °C. We investigated the solubilization of 15 drugs with varying pKa and partition coefficient (log P) values using these ILs and performed a comparative analysis. Furthermore, we present MGM-IL as a new skin permeation enhancer for the drug model flurbiprofen (FRP). We confirmed that AA/MGM-IL improves the skin permeation of FRP through hairless mouse skin. Moreover, AA/MGM-IL enhanced drug skin permeability by affecting keratin rather than stratum corneum lipids, as confirmed by ATR-FTIR. To conclude, MGM-ILs exhibited potential as drug solubilizer and skin permeation enhancers of drugs.

Xanthan Gum-based Food Thickeners Reduce Disintegration Time of Medical and OTC Loxoprofen Sodium Tablets

Xanthan gum-based food thickeners have been reported to potentially interfere with tablet disintegration. Loxoprofen sodium (LOX) is widely used as an antipyretic analgesic and is expected to provide rapid pain relief. In this study, we aimed to investigate the impact of a xanthan gum-based food thickener on LOX tablet disintegration. We used four different brands each of medical and OTC-LOX tablets, each containing 60 mg of LOX as the sole active ingredient. Depending on the brand, tablet hardness varied between 50.1-96.6 N and was not associated with the disintegration time. Disintegration times for medical tablets not immersed in the food thickener were 536±215, 621±159, 348±22, 369±42 s and for OTC tablets, were 358±20, 336±13, 292±13, 172±27 s. Immersion in the food thickener for 15 min reduced medical tablet disintegration time to 177±46 and 233±150 s (the third and fourth brands were disintegrated during immersion), and that for OTC tablets to 77±40, 75±110, and 37±85 s (the fourth brand was disintegrated during immersion). Despite each tablet containing different pharmaceutical additives, no correlation was found between disintegration time and presence of superdisintegrants. The OTC tablet with a light anhydrous silicic acid coating exhibited the shortest disintegration time. Thus, the disintegration time of LOX tablets is accelerated when immersed in the xanthan gum-based food thickener, potentially leading to rapid pain relief for patients.

Cellulose ether treatment inhibits amyloid beta aggregation, neuroinflammation and cognitive deficits in transgenic mouse model of Alzheimer’s disease

Alzheimer’s disease (AD) is an incurable, progressive and devastating neurodegenerative disease. Pathogenesis of AD is associated with the aggregation and accumulation of amyloid beta (Aβ), a major neurotoxic mediator that triggers neuroinflammation and memory impairment. Recently, we found that cellulose ether compounds (CEs) have beneficial effects against prion diseases by inhibiting protein misfolding and replication of prions, which share their replication mechanism with Aβ. CEs are FDA-approved safe additives in foods and pharmaceuticals. Herein, for the first time we determined the therapeutic effects of the representative CE (TC-5RW) in AD using in vitro and in vivo models. Our in vitro studies showed that TC-5RW inhibits Aβ aggregation, as well as neurotoxicity and immunoreactivity in Aβ-exposed human and murine neuroblastoma cells. In in vivo studies, for the first time we observed that single and weekly TC-5RW administration, respectively, improved memory functions of transgenic 5XFAD mouse model of AD. We further demonstrate that TC-5RW treatment of 5XFAD mice significantly inhibited Aβ oligomer and plaque burden and its associated neuroinflammation via regulating astrogliosis, microgliosis and proinflammatory mediator glial maturation factor beta (GMFβ). Additionally, we determined that TC-5RW reduced lipopolysaccharide-induced activated gliosis and GMFβ in vitro. In conclusion, our results demonstrate that CEs have therapeutic effects against Aβ pathologies and cognitive impairments, and direct, potent anti-inflammatory activity to rescue neuroinflammation. Therefore, these FDA-approved compounds are effective candidates for developing therapeutics for AD and related neurodegenerative diseases associated with protein misfolding.

Manganese Sulfate Nanocomposites Fabricated by Hot-Melt Extrusion for Chemodynamic Therapy of Colorectal Cancer.

The development of metal salts-based nanocomposites is highly desired for the Fenton or Fenton-like reaction-based chemodynamic therapy of cancer. Manganese sulfate (MnSO4)-dispersed nanoparticles (NPs) were fabricated with a hot-melt extrusion (HME) system for the chemodynamic therapy of colorectal cancer in this study. MnSO4 was homogeneously distributed in polyethylene glycol (PEG) 6000 (as a hydrophilic polymer) with the aid of surfactants (Span 80 and Tween 80) by HME processing. Nano-size distribution was achieved after dispersing the pulverized extrudate of MnSO4-based composite in the aqueous media. The distribution of MnSO4 in HME extrudate and the interactions between MnSO4 and pharmaceutical additives were elucidated by Fourier-transform infrared, X-ray diffractometry, X-ray photoelectron spectroscopy, and scanning electron microscopy analyses. Hydroxyl radical generation efficiency by the Fenton-like chemistry capability of Mn2+ ion was also confirmed by catalytic assays. By using the intrinsic H2O2 in cancer cells, MnSO4 NPs provided an elevated cellular reactive oxygen species level, apoptosis induction capability, and antiproliferation efficiency. The designed HME-processed MnSO4 formulation can be efficiently used for the chemodynamic therapy of colorectal cancer.

Pluronic® triblock copolymer-based nanoformulations for cancer therapy: A 10-year overview.

This paper provides a review of the literature on the use of Pluronic® triblock copolymers for drug encapsulation over the last 10years. A special focus is given to the progress of drug delivery systems (e.g., micelles, liposomes, micro/nanoemulsions, hydrogels and nanogels, and polymersomes and niosomes); the beneficial aspects of Pluronic® triblock copolymers as biological response modifiers and as pharmaceutical additives, adjuvants, and stabilizers, are also discussed. The advantages and limitations encountered in developing site-specific targeting approaches based on Pluronic-based nanostructures in cancer treatment are highlighted, in addition to innovative examples for improving tumor cytotoxicity while reducing side effects.

Characterization of Boswellia rivae Engl Resin as a Potential Use for Pharmaceutical Excipient.

Pharmaceutical excipients derived from natural sources like resins are nowadays meritoriously used in the formulation of drugs. Resins of natural origin have many advantages over chemically synthesized substances; they are safer, nontoxic, less expensive, biodegradable, and widely available. To our knowledge, resins from plants have been not sufficiently explored for application in pharmaceutical formulations. Thus, in the present study, a resin isolated from Boswellia rivae Engl was characterized for its potential use as a pharmaceutical excipient. Method. The resin was extracted from the oleo gum resin of Boswellia rivae Engl, which involved the removal of volatile oils, gum, and Boswellic acid contents. The dried resin powder was then characterized for its micromeritic properties, heavy metal contents, moisture content, moisture absorption power, pH, solubility, swelling property, and acute toxicity profile. Moreover, the crystal nature and the chemical functionality of the resin were evaluated by using X-ray diffraction and Fourier transform infrared spectrometry, respectively. Results. The yield of the neutral resin was 13.17%, and the powder was pale yellow and had irregular surfaces. The resin was freely soluble in organic solvents but almost insoluble in water. The moisture content of the dried extract was 2.5% while its moisture absorption capacity was 2.5%, 4%, and 5.47% at 40%, 60%, and 75% RH, respectively. Besides, the maximum swelling capacities of the resin observed were 40%, 37%, and 30% at 350C, 300C, and 250C, respectively. The bulk powder exhibited a 1.21 Hausner ratio, 36.497 angles of repose, and 17.03% Carr's index, indicating the fair flowability of the powder. Heavy metals such as zinc, chromium, and cobalt were detected at a low level while elements like copper, manganese, lead, and cadmium were absent. The X-ray diffraction study revealed that the crystallinity index of the powder was 42.7% with a crystal size of 994.5A. The Boswellia resin could be safe in mice up to 3 g/kg of their body weight. In conclusion, the physicochemical properties of the resin powder investigated reveal its potential application as pharmaceutical additives in the formulation of modified release solid dosages forms like tablets and microcapsules.

AUTOMATED FLOW INJECTION SPECTROPHOTOMETRIC DETERMINATION OF THE PROTON PUMP INHIBITOR OMEPRAZOLE IN PHARMACEUTICAL FORMULATIONS

A simple and fast flow-injection method for the determination of omeprazole in pharmaceutical preparations is proposed. Detection of the drug is based on the measurement of the absorption signals for the product resulting from the oxidation of omeprazole with N-bromosuccinimide in acidic medium. A flow rate of 0.5 ml/min was pumped and active material was detected at 370 nm. Limit of detection (LOD) and limit of quantitation (LOQ) were calculated to be 2.0 and 6.5 μg/ml, respectively. No interference was observed from common pharmaceutical additives. The method was successfully applied to the assay of omeprazole in capsule preparations and in spiked human plasma. The results were statistically compared with those of the official high-performance liquid chromatography (HPLC) method of the USP by applying Student’s t-test and F-test.

Biodegradation of diclofenac and ibuprofen in Fluidized Bed Reactor applied to sanitary sewage treatment in acidogenic and denitrifying conditions

The diclofenac (DCF) and ibuprofen (IBU) removal were assessed in an enlarged scale denitrifying Fluidized Bed Reactor (FBR), fed with sanitary sewage plus ethanol (74–100 mg L−1) and nitrate (89–136 mg L−1). The experiment was sectioned into four phases. In Phase I the Hydraulic Retention Time (HRT) was set in 18 ± 3 h without DCF and IBU addition and the FBR shows a heterotrophic denitrifying behavior with 97 % nitrate removal. In Phase II the addition of pharmaceuticals did not change COD and nitrate removal. In Phase III the HRT was decreased to 12 ± 1 h which did not influence denitrification but decreased the efficiency of DCF (35 %) and IBU (40 %) removal. In Phases I, II and III the removal of organic matter was limited by the concentration of influent nitrate. The HRT was then increased in Phase IV to 18 ± 2 h and nitrate was not added to the feeding; which led to denitrification no longer being the preferential route and replaced by acidogenic metabolism, evidenced by the highest concentration and diversity of total volatile fatty acids (VFA), resulting in increased organic matter removal efficiency (56 %), DCF (53 %), IBU (56 %) and ethanol (99.7 %). In Phase IV, acidogenic bacteria were mainly responsible for DCF and IBU degradation by ω and β-oxidation. This study establishes that DCF and IBU biodegradation in FBR applied to sanitary sewage treatment in denitrifying condition is overcome by acidogenic metabolism in the absence of nitrate as an electron acceptor, favoring the pharmaceuticals degradation.

New UPLC method development and validation for simultaneous estimation of netiputant and palonosetron using bulk and pharmaceutical dosage form using UPLC

A simple and selective LC method is described for the determination of Netupitant and Palonosetron in tablet dosage forms. Chromatographic separation was achieved on a Inertsil ODS (C18) RP Column (250mm x 4.6 mm. 5µm) column using mobile phase consisting of a 55 volumes of mixed phosphate buffer and 45 volumes of acetonitrile were prepared with detection of 253nm. Linearity was observed in the range 25-125 µg/ml for Netupitant (r 2 =0.995) and 50-150 µg /ml for Palonosetron (r 2 =0.999) for the amount of drugs estimated by the proposed methods was in good agreement with the label claim. The proposed methods were validated. The accuracy of the methods was assessed by recovery studies at three different levels. Recovery experiments indicated the absence of interference from commonly encountered pharmaceutical additives. The method was found to be precise as indicated by the repeatability analysis, showing %RSD less than 2. All statistical data proves validity of the methods and can be used for routine analysis of pharmaceutical dosage form.

Cytotoxic effects of CeO2 NPs and β-Carotene and their ability to induce apoptosis in human breast normal and cancer cell lines

Cerium Oxide Nanoparticles (CeO2 NPs) and β-carotene are natural-source products that have recently gained an increased interest as pharmaceutical additives because of their effectiveness in living systems, but the behavior of these substances varies according to factors and conditions. The above mentioned materials were evaluated in breast normal (HBL-100) and cancer cell lines (CAL-51 and MCF-7 ) by different techniques ; MTT assay for studying cytotoxic effects, morphological changes, sqPCR, including gene expression of caspases 8 and 9, and P53. All experiments were conducted on cell lines by the use of the materials alone as well as their combination. The results of the MTT assay showed that the two materials (CeO2 NPs and β-carotene) had a toxic effect on the cell lines, and the toxicity of the materials was concentration-dependent. The half maximal inhibitory concentration (IC50) values of CeO2 NPs and β-Carotene, as observed by the effects in all cell lines, have significant differences. Our findings showed that CeO2 NPs has a higher toxicity on the HBL-100 and MCF-7 cell lines compared with β-Carotene. The toxic effects of each material alone and combined together were reflected on cell morphology by the appearance of irreversible cytopathic changes in the treated cells. The two materials had the ability to cause cellular death and DNA damage, inducing the external pathway of apoptosis. A significant increase in the gene expression of caspase 8 appeared at P≤0.05. Collectively, the CeO2 NPs and β-Carotene have an inhibitory effect on both breast cancer and normal cell lines. We conclude the both materials have genotoxic effects on normal and cancer cell lines.

Lipids, Chloroform, and Their Intertwined Histories

Lipids and their fatty acid constituents, in particular, have been the subject of academic and industrial research initiatives since their isolation by Michel-Eugène Chevreul in 1813. Fatty acids can be saturated or unsaturated, their physical properties depending on the aliphatic chain length and degree of saturation. They constitute the building blocks of many lipid groups, such as triglycerides and phospholipids; are key additives in commercial foods, pharmaceuticals, and cosmetics; and can cross cell membranes. Chloroform was synthesized in 1831 by Samuel Guthrie and has had a tortuous history of interactions with mankind: from an anesthetic in obstetrics, dentistry, and surgery, to being labeled as a potential carcinogen in the 1970s. It has also had important nonmedical applications, such as in chemical engineering mass transfer systems designed to estimate binary gas diffusion coefficients. Although chemically dissimilar, lipids and chloroform intertwined their scientific paths through the work of Jordi Folch and associates in the 1940s-1950s, in which many lipid-based brain molecules were isolated and characterized. This article outlines the separate histories of lipids and chloroform, and those research initiatives in which they have acted synergistically. The narrative covers the interplay of chemical compounds with different historical backgrounds, but with physical properties which continue to foster their modern-day interaction.

Development of a simple validated spectrofluorometric method for the assay of midodrine in tablets dosage form; Application to content uniformity testing

A new sensitive spectrofluorimetric technique has been established for the estimation of midodrine hydrochloride. This method depends on the condensation reaction of ortho-phthalaldehyde with the primary aliphatic amine of midodrine in the presence of 2-mercapto-ethanol. The pH of the medium was adjusted to 9.0 using 0.1 M borate buffer. The fluorescence of the product was measured at wavelength of 451 nm after excitation at 334 nm. The method was rectilinear over a concentrations range of 0.1 to 1.5 µg mL−1. The lower detection and quantitation limits were 31 and 94 ng mL−1, respectively. The method was investigated following the guidelines of the International Council of Harmonization. Analysis of commercial tablet dosage form was carried out successfully by the current method with excellent recovery percentages and with no influence from coexisted pharmaceutical additives .This method was used to evaluate the uniformity of the contents of commercial tablets according to the United States Pharmacopoeia.

Investigating demyelination, efficient remyelination and remyelination failure in organotypic cerebellar slice cultures: Workflow and practical tips.

Healthy myelin is essential for proper brain function. When the myelin sheath is damaged, fast saltatory impulse conduction is lost and neuronal axons become vulnerable to degeneration. Thus, regeneration of the myelin sheath by encouraging oligodendrocyte lineage cells to remyelinate the denuded axons is a promising therapeutic target for demyelinating diseases such as multiple sclerosis. Ex vivo organotypic cerebellar slice cultures are a useful model to study developmental myelination, demyelination, remyelination and remyelination failure. In these cultures, the cerebellum's three-dimensional architecture and various cell populations remain largely intact, providing a realistic and relatively cost-efficient model that can be easily manipulated by the addition of viral vectors, pharmaceuticals or (transgenic) cells to augment or replace resident cell populations. Moreover, slice cultures can be treated with lysolecithin or polyinosinic:polycytidylic acid to induce demyelination and mimic efficient as well as inefficient remyelination. It can be challenging to set up slice cultures for the first time, as in our experience, seemingly minor differences in technique and materials can make a great difference to the quality of the cultures. Therefore, this report provides an in-depth description for the generation and maintenance of ex vivo organotypic cerebellar cultures for demyelination-remyelination studies with a focus on practical tips for scientists that are new to this technique.

A method for identifying the manufacturer of sleeping pills used in crime via the analysis of pharmaceutical additives

A method for identifying the manufacturer of sleeping pills used in crime via the analysis of pharmaceutical additives

Adulteration of Weight Loss Supplements by the Illegal Addition of Synthetic Pharmaceuticals.

Weight loss supplements that have illegal additives of pharmaceutical drugs or analogues have additional health risks, and customers may not be aware of what they are taking. This research is an essential investigation and quantification of illegally added pharmaceuticals or prescription medications, specifically fluoxetine, phenolphthalein, and sibutramine, in herbal weight loss supplements offered for sale in the United Arab Emirates (UAE). In this case, 137 weight loss supplements were collected and analyzed in this study. Reversed-phase high-performance liquid chromatography with UV absorption detection coupled to tandem mass spectrometry (RP-HPLC-MS/MS) analyses were used to determine the presence of the pharmaceutical chemicals. Among the weight loss supplements, 15.3% (95% CI: 9.2–21.4) contained undeclared sibutramine, 13.9% (95% CI: 8.01–19.7) contained undeclared phenolphthalein, and 5.1% (95% CI: 1.4–8.8) contained undeclared fluoxetine. Amongst all weight loss supplements, 17.5% (95% CI: 11.07–24) contained significant concentrations of either sibutramine, phenolphthalein, or fluoxetine. Whilst weight loss herbal supplements offered for sale in the UAE have relatively low percentages of undeclared pharmaceuticals, many people take several different supplements daily and may encounter quite high levels of combined exposure to toxic compounds.

Degradation and inactivation efficacy of ozone water for antineoplastic drugs in hospital settings.

Occupational exposure to antineoplastic drugs in hospital settings is recognized to be hazardous, and as such environmental decontamination including degradation and inactivation of such drugs is recommended. To data, although various agents such as oxidants have been reported to be useful for decontamination, simpler, safer, and more convenient methods are required. In this study, the degradation and inactivation efficacy of ozone water, which has newly been introduced for decontamination of antineoplastic drugs in spills, was investigated for formulations of gemcitabine, irinotecan, and paclitaxel. Antineoplastic formulations (medicinal ingredient: ∼1.5 μmol) were mixed with 50 mL of ozone water (>4 mg/L). The reactions were monitored by high-performance liquid chromatography, and the degradation mixtures were analyzed by 1H nuclear magnetic resonance spectroscopy in order to obtain the structural information of the degradation products. The formulations of gemcitabine and irinotecan and those degradation mixtures were evaluated for their mutagenicity using the Ames test and cytotoxicity against human cancer cells. gemcitabine and irinotecan were found to be readily degraded by the ozone treatment, and their active sites were suggested to be degraded. In contrast, paclitaxel was hard to be decomposed, possibly owing to the consumption of ozone by the polyoxyethylene castor oil added as a pharmaceutical additive of the formulation. No significant mutagenic changes of Salmonella typhimurium strains used for the Ames test were observed for the samples within the concentration ranges examined. The ozone treatment showed obvious increases in cell viability for gemcitabine formulation, and mild increases for irinotecan formulation. Ozone water was shown to be effective as a decomposition agent for the antineoplastic drug formulations examined, although the efficacy depends on the chemical structures of the drugs and the pharmaceutical additives. It was also suggested that ozone treatment has a tendency to decrease the toxicity of the antineoplastic drug formulations. As such, further studies are required in order to clarify the effects and application limitations of ozone water.

Rapid screening of 16 illicit additives in herbal pharmaceuticals and health foods based on ion mobility spectrometry

A qualitative screening method using ion mobility spectrometry (IMS) was developed for the detection of 16 commonly found illicit additives in herbal pharmaceuticals and health foods, including ibuprofen, nitrazepam, nitrendipine, indomethacin, phenobarbital, sibutramine, diclofenac sodium, diazepam, estazolam, melatonin, phenolphthalein, prednisone acetate, betamethasone, metformin HCl, glibenclamide, and tadalafil. A substance database suitable for the rapid on-site analysis of these compounds was then established based on the matching algorithm of some key parameters, such as reduced mobility calculated and tolerance estimated, etc. The developed measurement was successfully applied to assess 15 real samples after full validation in respect of sensitivity, matrix effect, recovery, precision, and stability. The suspected illicit additives were all consistently confirmed and further quantified with high-performance liquid chromatography (HPLC). Two sampling introduction methods of direct swabbing with swab paper and a simple extraction procedure with methanol were also compared, and no significant difference was found.

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. However, the addition of HPMC polymer markedly suppressed the crystal growth, providing both improved drug stability and profound dissolution profile. Raman spectrometry denoted the inter-molecular hydrogen boding between MTK particle and HPMC polymer. The crystal growth or dissolution profile of MSs was markedly affected by pharmaceutical additives (sucrose or simethicone) in the preparations or storage temperature. The optimized HPMC-based MS exhibited over 80% higher bioavailability, compared to marketed granule (Singulair®) in rats. Therefore, novel MTK-loaded MS can be a promising liquid preparation, bettering oral absorption and patient's compliance.