Development of a novel direct compressible co-processed excipient and its application for formulation of Mirtazapine orally disintegrating tablets.

INTRODUCTION: Orally disintegrating tablets (ODTs) are designed to dissolve in the oral cavity within 3 min, providing a convenient option for patients as they can be taken without water. Direct compression is the most common method used for ODTs formulations. However, the availability of single composite excipients with desirable characteristics such as good compressibility, fast disintegration, and a good mouthfeel suitable for direct compression is limited. OBJECTIVE: This research was proposed to develop a co-processed excipient composed of xylitol, mannitol, and microcrystalline cellulose for the formulation of ODTs. METHODS: A total of 11 formulations of co-processed excipients with different ratios of ingredients were prepared, which were then compressed into ODTs, and their characteristics were thoroughly examined. The primary focus was on evaluating the disintegration time and hardness of the tablets, as these factors are important in ensuring the ODTs meet the desired criteria. The model drug, Mirtazapine was then incorporated into the chosen optimized formulation. RESULTS: The results showed that the formulation comprised of 10% xylitol, 10% mannitol and 80% microcrystalline cellulose demonstrated the fastest disintegration time (1.77 ± 0.119 min) and sufficient hardness (3.521 ± 0.143 kg) compared to the other formulations. Furthermore, the drug was uniformly distributed within the tablets and fully released within 15 min. CONCLUSION: Therefore, the developed co-processed excipients show great potential in enhancing the functionalities of ODTs, offering a promising solution to improve the overall performance and usability of ODTs in various therapeutic applications.

de novo transcriptome assembly for discovering gene expressed in Holothuria leucospilota with exposed to copper.

Sea cucumber is a bioremediator as it can composite organic matter and excrete inorganic matter. Sea cucumber has the potential to serve as a bioindicator in marine habitat as they provide an integrated insight into the status of their environment over long periods. Sea cucumbers are sensitive to the organic concentration in the marine environment and can effectively provide an early warning system for any organic contamination that can negatively impact the ecosystem. The availability of a reference transcriptome for sea cucumber would constitute an essential tool for identifying genes involved in crucial steps of the defence pathway. De novo assembly of RNA-seq data enables researchers to study the transcriptomes without needing a genome sequence. In this study, sea cucumbers fed with Kappaphycus alvarezii powder were treated with 0.20 mg/L copper concentration comprehensive transcriptome data containing 75,149 Unigenes, with a total length of 20,460,032 bp. A total of 8820 genes were predicted from the unigenes, annotated, and functionally categorized into 25 functional groups with approximately 20% cluster in signal transduction mechanism. The reference transcriptome presented and validated in this study is meaningful for identifying a wide range of gene(s) related to the bioindication of sea cucumber in a high copper environment.

Cassia alata, Coriandrum sativum, Curcuma longa and Azadirachta indica: Food Ingredients as Complementary and Alternative Therapies for Atopic Dermatitis-A Comprehensive Review.

Traditional medicine is critical in disease treatment and management. Herbs are gaining popularity for disease management and treatment. Therefore, they can be utilised as complementary and alternative treatment (CAT) ingredients. Atopic dermatitis (AD) is one of the common non-communicable diseases. It is characterised by chronic inflammatory skin disease with intense pruritus and eczematous lesions. AD is associated with oxidative stress, microbial infection, and upregulation of inflammatory cytokines. Both children and adults could be affected by this skin disorder. The prevalence of AD is increasing along with the country's level of development. This review revisited the literature on four medicinal herbs widely used as complementary medicine to manage AD. These therapeutic herbs are commonly eaten as food and used as spices in Asian cuisine. The four food herbs reviewed are Cassia alata, Coriandrum sativum, Curcuma longa Linn, and Azadirachta indica. Their traditional uses and phytochemical content will be covered. Four relevant pharmacological and biological activities of the plants crucial in AD management have been reviewed and discussed, including anti-inflammatory, anti-microbial, antioxidant, and wound recovery.

Anti-methicillin-resistance Staphylococcus aureus (MRSA) compounds from Bauhinia kockiana Korth. And their mechanism of antibacterial activity.

BACKGROUND: Bauhinia kockiana originates from Peninsular Malaysia and it is grown as a garden ornamental plant. Our previous study reported that this plant exhibited fairly strong antioxidant and antimicrobial activities. This paper focused on the assessment of the antibacterial activity of B. kockiana towards methicillin-resistance Staphylococcus aureus (MRSA), to purify and to identify the antibacterial compounds, and to determine the mechanism of antibacterial activity. METHODS: Antibacterial activity of B. kockiana flower was evaluated qualitatively and quantitatively using disc diffusion assay and microbroth dilution method. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of extracts were examined. Phytochemical analysis was performed to determine the classes of phytochemicals in the extracts. Bioactivity guided isolation was employed to purify the antibacterial agents and identified via various spectroscopy methods. Scanning electron microscopy (SEM) technique was used to evaluate the antibacterial mechanism of extract and compounds isolated. RESULTS: B. kockiana flower was found to exhibit fairly strong antibacterial activity towards both strains of MRSA bacteria used, MIC varies from 62.5-250 µg/mL. Tannins and flavonoids have been detected in the phytochemical analysis. Gallic acid and its ester derivatives purified from ethyl acetate extract could inhibit MRSA at 250-500 µg/mL. SEM revealed that the cells have undergone plasmolysis upon treatment with the extract and compounds. CONCLUSION: Tannins and polyphenols are the antibacterial components towards MRSA in B. kockiana. Massive leakage of the cell content observed in treated cells showed that the phytochemicals have changed the properties of the cell membranes. Amphiphilic nature of the compounds exhibited the antibacterial activity towards MRSA via three stages: (1) cell membrane attachment; (2) cell membrane fluidity modification; and (3) cell membrane structure disruption.

Compounding and Characterization of Oral Disintegrating Films Containing Memantine Hydrochloride for Geriatrics.

Memantine hydrochloride is commonly prescribed for Alzheimer's disease and vascular dementia. However, the drug is only available in tablet form, a dosage form which is difficult for geriatrics to swallow. This problem is especially difficult for those patients diagnosed with Alzheimer's. This study was therefore aimed to develop and characterize an oral disintegrating film containing memantine hydrochloride using different types and concentrations of polymers. Using the solvent casting method, twelve formulations were developed, which involved manipulations on the type and concentration of the polymer. Afterwards, six formulations were selected to undergo characterization tests. These tests evaluated the films' tensile strength, Young's Modulus, percent elongation, folding endurance, disintegration and dissolution time, content uniformity, moisture loss, and moisture uptake. Polymers such as polyvinyl alcohol, hydroxypropyl methylcellulose, polyvinyl pyrrolidone, and pullulan gum were respectively incorporated at different concentrations. The study found that only hydroxypropyl methylcellulose and polyvinyl alcohol formulations developed into acceptable oral disintegrating films. Formulation E (hydroxypropyl methylcellulose 50-mg/film), which exhibited optimal mechanical strength, fast disintegration and dissolution, and excellent content uniformity, was identified as the best formula. Although polyvinyl alcohol showed higher mechanical strength, hydroxypropyl methylcellulose films were better at fulfilling the optimal characteristics of an oral disintegrating film. The study showed that the mechanical strength increased proportionally to the polymer concentration in the polyvinyl alcohol film. However, for the hydroxypropyl methylcellulose film, the mechanical strength increased only when hydroxypropyl methylcellulose's concentration was increased from a 40-mg/film to a 50-mg/film but decreased with a 60-mg/film. To summarize, orally disintegrating films containing memantine hydrochloride was developed, characterized, and reasoned to have high potential to be marketed and to increase medication compliance among geriatrics suffering from Alzheimer's disease.

Development of a Novel Co-processed Excipitient Comprising of Xylitol, Mannitol, Microcrystalline Cellulose, and Crospovidone for the Compounding of Memantine Hydrochloride Orally Disintegrating Tablet.

Orally disintegrating tablets, which were originally developed in the pharmaceutical field to improve the compliance of patients who had difficulty swallowing tablets, have become a preferable choice in solid dosage forms since it brings advantages to the patients and consumers in the healthcare system. Among the advantages of this novel dosage form are a faster onset of action, improved bioavailability, and the ease of administration as it can be taken without water. However, there are still some limitations of orally disintegrating tablets that need to be overcome, including a lack of mechanical strength, an unpleasant taste of the drug in the mouth, and a stability issue due to its hygroscopicity nature. This objective of this study was to identify the composition of co-processed excipients comprising of mannitol, microcrystalline cellulose, xylitol, and crospovidone or croscarmellose sodium in order to formulate orally disintegrating tablets containing memantine hydrochloride. This study was carried out in two stages. Firstly, orally disintegrating tablets containing memantine hydrochloride with 6 different formulations, which differed in the percentage of crospovidone or croscarmellose sodium, were formulated and manufactured. Secondly, the orally disintegrating tablets obtained were evaluated through pre- and post-compression tests based on the standard for orally disintegrating tablets. Formulation 3, which consisted of 10% xylitol, 10% mannitol, 72% microcrystalline cellulose, and 8% crospovidone, was chosen as the optimum formulation for the co-processed excipient since it was the fastest disintegration process among all the formulations in the study. In addition, Formulation 3 also showed the acceptable and satisfying results in other evaluation tests such as - weight variation test, hardness test, and friability test. The co-processed excipient comprising of 10% xylitol, 10% mannitol, 72% microcrystalline cellulose, and 8% crospovidone, which is characterized by improved functionalities such as a fast disintegration process, plays a crucial role in the application of orally disintegrating tablets.

Optimization of a Luteolin-Loaded TPGS/Poloxamer 407 Nanomicelle: The Effects of Copolymers, Hydration Temperature and Duration, and Freezing Temperature on Encapsulation Efficiency, Particle Size, and Solubility.

BACKGROUND: Luteolin is a flavonoid compound that has been widely studied for its various anti-cancer properties and sensitization to multidrug-resistant cells. However, the limited solubility and bioavailability of Lut hindered its potential clinical use. Theoretically, the combination of this compound with vitamin E TPGS and poloxamer 407 can produce a synergistic effect to enhance tumor apoptosis and P-glycoprotein inhibition. This study aimed to develop and optimize vitamin E TPGS/Poloxamer 407 micelles loaded with luteolin through investigating certain factors that can affect the encapsulation efficiency and particle size of the micelle. METHODS: A micelle was prepared using the film hydration method, and the micellar solution was lyophilized. The cake formed was analyzed. The factors investigated include the concentrations of the surfactants, ratio of vitamin E TPGS/Poloxamer 407, temperature of the hydrating solution, duration of hydration, and freezing temperature before lyophilization. The effects of these factors on the encapsulation efficiency and particle size of the micelle were also studied. The encapsulation efficiency was measured using a UV-Vis spectrophotometer, while particle size was measured using dynamic light scattering. RESULTS: The optimized micelle was found to have 90% encapsulation efficiency with a particle size of less than 40 nm, which was achieved using a 10% concentration of surfactants at a vitamin E TPGS/Poloxamer 407 ratio of 3:1. The optimized temperature for hydrating the micellar film was 40 °C, the optimized mixing time was 1 h, and the optimized freezing temperature was -80 °C. The solubility of the luteolin-loaded micelles increased 459-fold compared to pure Lut in water. The critical micelle concentration of the vitamin E TPGS/Poloxamer 407 micelle was 0.001 mg/mL, and the release study showed that luteolin-loaded micelles exhibited sustained release behavior. The release of luteolin from a micelle was found to be higher in pH 6.8 compared to pH 7.4, which signified that luteolin could be accumulated more in a tumor microenvironment compared to blood. CONCLUSION: This study demonstrated that several factors need to be considered when developing such nanoparticles in order to obtain a well-optimized micelle.

Self-Assessment of INTERHEART Risk Stratification among the Middle-Aged Community in Malaysia.

Research background and Objectives: Age is an independent risk factor for cardiovascular disease (CVD), but CVD risk factors are preventable, and lack of awareness of its risk factors is a contributing factor to CVDs. Middle-aged people may be more likely to engage in unhealthy lifestyle behaviours which can increase the risk of CVD. Health self-assessment is crucial for early detection and management of health issues and early lifestyle intervention for better personalised health management. This study aims to determine the self-assessment of INTERHEART risk classification among the middle-aged community in Malaysia. Method: Local community members aged 40-60 years and who are currently residing in Malaysia were recruited via non-randomised sampling. Sociodemographic characteristics and dietary pattern related to salt, fibre, fat (deep fried/snacks), poultry/meat intakes, and other cardiovascular risk factors (waist-hip ratio, medical history related to diabetes/hypertension, history/exposure of tobacco use, psychosocial status, and level of physical activity) were assessed; INTERHEART risk scores were then computed and stratified into low, medium and high risks. Results: Approximately 45% (n = 273/602) of middle-aged respondents in Malaysia are at moderate-to-high risk of cardiovascular events, with men being more likely to develop CVD compared to women. The results of the survey indicated that poultry/meat intake (61%), physical inactivity (59%), and second-hand smoke (SHS) exposure (54%) are the most prevalent risk factors among the respondents. One-third of the respondents consumed excessive salty food and deep fried foods/snacks/fast food, and only one-third of them consumed vegetables/fruits at a recommended level. It is worrying that about a quarter of the respondents felt several periodical/permanent stresses and even felt sad/blue/depressed for two weeks or more in a row. Males, labour workers, and those with lower educational levels are more likely to develop CVD events. Conclusions: This study found that 45% of the middle-aged respondents were having moderate-to-high risk for cardiovascular events with multiple risk factors related to unhealthy lifestyle habits and environmental factors. In addition to non-modifiable factors such as gender and age, sociodemographic factors, i.e., educational level and occupation, are equally important factors to determine CVD risk. Overall, the findings of this study emphasize the clinical relevance of assessing multiple factors in the determination of CVD risks for early prevention and management of cardiovascular diseases.

Natural alternatives from your garden for hair care: Revisiting the benefits of tropical herbs.

Hair shampoos containing botanical ingredients without synthetic additives, such as parabens, petrochemicals, sulfates and silicones are more skin- and environmentally friendly. In recent years, there is a growing demand for shampoo products with botanical extracts. Shampoos with botanical extracts are well-known for their perceived health benefits. They are also generally milder, non-toxic, natural, and less likely to disrupt the hair and scalp's natural pH and oil balance. Many also believe that shampoos with botanical origins have higher standards of quality. Numerous botanical extracts had been used as natural active ingredients in cosmetic formulations to meet consumer demands. In this review, we have revisited six tropical plants commonly added as natural active ingredients in shampoo formulations: Acacia concinna, Camellia oleifera, Azadirachta indica, Emblica officinalis, Sapindus mukorossi, and Garcinia mangostana. These plants have been traditionally used for hair care, and scientific research has shown that they exhibit relevant physicochemical properties and biological activities that are beneficial for hair care and scalp maintenance.

Application of Co-processed Excipient as a Novel Method to Compound Orally Disintegrating Tablets.

Co-processed excipients were prepared by incorporating one excipient into the particle structure of another and a combination of two or more compendia or noncompendia excipients to physically modify their properties, which cannot be achievable by simple physical mixing. The co-processed multicomponent-based excipients were introduced to achieve better characteristics and tableting properties. This objective of this study was to develop and evaluate a co-processed excipient for amlodipine orally disintegrating tablets to simplify the compounding process. The co-processed excipients were prepared by wet granulation with 5% of polyvinylpyrrolidone and croscarmellose sodium, five different percentages of microcrystalline cellulose, and lactose monohydrate. After sieving and drying, the co-processed excipients were evaluated for flowability and compressibility. The co-processed excipients were mixed with the amlodipine powder and magnesium stearate and compressed into tablets. The amlodipine tablets were evaluated for weight variation, content uniformity, thickness, hardness, friability, disintegration, and dissolution tests. Formulation 4 was chosen as the optimum formulation because the results showed this formulation had the excellent flowability and compressibility of a co-processed excipient. It showed uniformity of weight, content, thickness, and hardness, weight loss less than 1%, fast disintegration time, and dissolution results. The developed co-processed excipient can be used by the pharmaceutical industry in the future to compound amlodipine orally disintegrating tablets in a fast and economical way.

Assessment of phytochemical content, polyphenolic composition, antioxidant and antibacterial activities of Leguminosae medicinal plants in Peninsular Malaysia.

BACKGROUND: Many medicinal plants from Leguminosae family can be found easily in Malaysia. These plants have been used as traditional medicines by local ethnic groups, where they are prepared as decoction, pastes for wound infections, and some have been eaten as salad. This paper focused on the assessment of antioxidant potential, antibacterial activity and classes of phytochemicals of nine plants from the Leguminosae family. METHODS: Acacia auriculiformis, Bauhinia kockiana, Bauhinia purpurea, Caesalpinia pulcherrima, Calliandra tergemina, Cassia surattensis, Leucaena leucocephala, Peltophorum pterocarpum, and Samanea saman were extracted with aqueous methanol and dichloromethane:methanol mixture to test for antioxidant and antibacterial activities. The Folin-Ciocalteu assay was conducted to quantify the total phenolic content and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) assay was used to determine the free radical quenching capacity. Antibacterial activity was assessed using disc diffusion (Kirby-Bauer) assay. Screening for major classes of phytochemical was done using standard chemical tests. RESULTS: B. kockiana flowers and C. pulcherrima leaves contained high total phenolic content (TPC) and strong DPPH radical scavenging ability with TPC of 8280 ± 498 mg GAE/100 g, IC(50) of 27.0 ± 5.0 µg/mL and TPC of 5030 ± 602 mg GAE/100 g, IC(50) of 50.0 ± 5.0 µg/mL respectively. Positive correlation was observed between TPC and free radical scavenging ability. Most extracts showed antibacterial activity against Gram positive bacteria at 1 mg, while none showed activity against Gram negative bacteria at the same dose. All extracts (except Samanea saman flower) showed antibacterial activity against two strains of methicillin resistant Staphylococcus aureus (MRSA) with MID values ranging between 100 µg/disc and 500 µg/disc. CONCLUSION: The potential source of antioxidant and antibacterial agents, especially for MRSA infection treatments were found in B. kockiana, C. pulcherrima, C. tergemina and P. pterocarpum. These preliminary results would be a guide in the selection of potential candidates for further pharmacological study and in search of new drug candidate in treating MRSA infections.

Choices of chromatographic methods as stability indicating assays for pharmaceutical products: A review.

Stability indicating assay describes a technique which is used to analyse the stability of drug substance or active pharmaceutical ingredient (API) in bulk drug and pharmaceutical products. Stability indicating assay must be properly validated as per ICH guidelines. The important components in a stability indicating assay include sensitivity, specificity, accuracy, reliability, reproducibility and robustness. A validated assay is able to measure the concentration changes of drug substance/API with time and make reliable estimation of the quantity of the degradation impurities. The drug substance is separated and resolved from the impurities. Pros and cons of HPLC, GC, HPTLC, CE and SFC were discussed and reviewed. Stability indicating assay may consist of the combination of chromatographic separation and spectroscopic detection techniques. Hyphenated system could demonstrate parallel quantitative and qualitative analysis of drug substances and impurities. Examples are HPLC-DAD, HPLC-FL, GC-MS, LC-MS and LC-NMR. The analytes in the samples are separated in the chromatography while the impurities are chemically characterised by the spectroscopy in the system. In this review, various chromatographic methods which had been employed as stability indicating assays for drug substance and pharmaceutical formulation were systematically reviewed, and the application of hyphenated techniques in impurities characterisation and identification were also discussed with supporting literatures.

Prevalence of Atopic Dermatitis and Pattern of Drug Therapy in Malaysian Children.

BACKGROUND: Atopic dermatitis (AD) is a chronic relapsing, noncontagious skin inflammation characterized by dry skin and itch. Mutation in filaggrin gene leads to defective skin barrier, allowing entry of allergen and eliciting immunological response. OBJECTIVES: The aims of this study were to investigate the prevalence of AD in Malaysian children and to understand the pattern of drug therapy. Such information could be useful to establish the relationship between ethnicity and family history of atopy and the development of associated signs and symptoms. METHODS: A cross-sectional survey was conducted among children attending kindergartens and nurseries. Standardized questionnaires were filled out by parents. RESULTS: Overall prevalence of AD was 13.4%. Of 384 participants recruited, the highest prevalence was observed in males, Malays, participants younger than 2 years, and those with atopic background such as asthma, hay fever, and family history of atopic diseases. Calamine and white soft paraffin were the preferred choice of nonprescription drugs, whereas topical hydrocortisone seemed to be the preferred choice of prescription drug in the management of AD. CONCLUSIONS: The overall prevalence is comparable to that reported in the International Study of Asthma and Allergies in Childhood Phase One. There is an association between ethnicity and AD prevalence. Topical corticosteroids and emollients are the mainstay of AD management among Malaysians.

Bioactivity-guided isolation of anticancer agents from Bauhinia kockiana Korth.

BACKGROUND: Flowers of Bauhinia kockiana were investigated for their anticancer properties. METHODS: Gallic acid (1), and methyl gallate (2), were isolated via bioassay-directed isolation, and they exhibited anticancer properties towards several cancer cell lines, examined using MTT cell viability assay. Pyrogallol (3) was examined against the same cancer cell lines to deduce the bioactive functional group of the phenolic compounds. RESULTS: The results showed that the phenolic compounds could exhibit moderate to weak cytotoxicity towards certain cell lines (GI50 30 - 86 µM), but were inactive towards DU145 prostate cancer cell (GI50 > 100 µM). CONCLUSION: It was observed that pyrogallol moiety was one of the essential functional structures of the phenolic compounds in exhibiting anticancer activity. Also, the carboxyl group of compound 1 was also important in anticancer activity. Examination of the PC-3 cells treated with compound 1 using fluorescence microscopy showed that PC-3 cells were killed by apoptosis.