Cocoa Butter: Evolution from Natural Food Ingredient to Pharmaceutical Excipient and Drug Delivery System.

For decades, cocoa butter has been extensively used in food industries, particularly in the production of chocolate confectioneries. The composition of fats within cocoa butter, such as stearic acid, palmitic acid, and oleic acid, determines its properties. Studies have indicated the existence of at least six polymorphic forms of cocoa butter, each possessing distinct characteristics and melting points. Recently, cocoa butter has garnered attention for its potential as a delivery system for pharmaceutical products. This review thoroughly explores cocoa butter, encompassing its production process, composition, properties, and polymorphism. It delves into its diverse applications across various industries including food, cosmetics, and pharmaceuticals. Additionally, the review investigates cocoa butter alternatives aiming to substitute cocoa butter and their roles in different drug delivery systems. The unique properties of cocoa butter have sparked interest in pharmaceutical industries, particularly since its introduction as a drug delivery system and excipient. This has prompted researchers and industry stakeholders to explore novel formulations and delivery methods, thereby expanding the range of options available to consumers in the pharmaceutical market.

Niacinamide: a review on dermal delivery strategies and clinical evidence.

Niacinamide, an active form of vitamin B3, is recognised for its significant dermal benefits including skin brightening, anti-ageing properties and the protection of the skin barrier. Its widespread incorporation into cosmetic products, ranging from cleansers to serums, is attributed to its safety profile and proven efficacy. Recently, topical niacinamide has also been explored for other pharmaceutical applications, including skin cancers. Therefore, a fundamental understanding of the skin permeation behaviour of niacinamide becomes crucial for formulation design. Given the paucity of a comprehensive review on this aspect, we provide insights into the mechanisms of action of topically applied niacinamide and share the current strategies used to enhance its skin permeation. This review also consolidates clinical evidence of topical niacinamide for its cosmeceutical uses and as treatment for some skin disorders, including dermatitis, acne vulgaris and actinic keratosis. We also emphasise the current exploration and perspectives on the delivery designs of topical niacinamide, highlighting the potential development of formulations focused on enhancing skin permeation, particularly for clinical benefits.

Effects of polyol and surfactant plasticisers on lyophilised rice starch wafers for buccal drug delivery.

Rice starch is a promising biopolymer for buccal formulations but typical oven drying may promote starch retrogradation that affects mechanical properties. Hence, lyophilisation was proposed here to improve starch product's stability. This study aims to investigate the effects of plasticisers (sorbitol and Tween® 80, T80) on the characteristics and drug release profiles of lyophilised rice starch wafers incorporated with propranolol hydrochloride. The wafers were prepared by lyophilising starch mixture (5%w/v) with plasticiser (0.2 and 0.3 g/g) and drug (10, 20, 30%w/w). Control wafers exhibited loose layers with rough wrinkled surface. Sorbitol resulted in a dense structure with higher puncture strength (PS) but lower water absorption capacity (WAC) while T80 loosened the flakes that reduced PS and increased WAC. Drug inclusion decreased PS and increased WAC of unplasticised wafers. T80-plasticised wafers with drug had a lower PS and higher WAC than sorbitol-plasticised wafers. Particularly, T80-plasticised wafers achieved outstandingly high PS and the lowest WAC at 30%w/w drug. Drug dissolution of wafers relied mainly on the drug crystallinity and WAC at 10 and 30%w/w drug. Plasticisers reduced and increased drug dissolution at 10 and 20%w/w drug, respectively. This study highlights the potential of lyophilisation in preparing rice starch wafers for buccal delivery.

Glycols: The ubiquitous solvent for dermal formulations.

Glycols stand out as one of the most commonly employed safe and effective excipients for pharmaceutical and cosmeceutical products. Their widespread adoption can be attributed to their exceptional solvency characteristics and their ability to interact effectively with skin lipids and keratin for permeation enhancement. Notably, propylene glycol enjoys significant popularity in this regard. Ongoing research endeavours have been dedicated to scrutinising the impact of glycols on dermal drug delivery and shedding light on the intricate mechanisms by which glycols enhance skin permeation. This review aims to mitigate the discordance within the existing literature, assemble a holistic understanding of the impact of glycols on the percutaneous absorption of active compounds and furnish the reader with a profound comprehension of the foundational facets pertaining to their skin permeation enhancement mechanisms, while simultaneously delving deeper into the intricacies of these processes.

Diversity of Asian skin: A review on skin biophysical properties.

Asian is home to dozens of different ethnic groups that are characterised by fascinating social and cultural variations. Unfortunately, existing literature on the skin properties of Asians tends to group this diverse population solely based on skin colour, perpetuating the misconception and stereotype that all Asian skin is the same. While Asia is one of the largest continents in the world, the difference in the geographical location and climate have long shaped the population into various ethnic groups with significant differences in the collective and diverse customs, traditions, cultures and living habits. The diverse ethnic groups in this region hint us that their skin biophysical characteristics can be very different from each other. This review features the profiling of the distinctive skin biophysical properties of Asians. We learn more about the different ethnic groups in Asia and acknowledge the unique skin biophysical properties even from the same country.

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.

Chitosan-based drug delivery systems for skin atopic dermatitis: recent advancements and patent trends.

Atopic dermatitis (AD) is a complex, relapsing inflammatory skin disease with a considerable social and economic burden globally. AD is primarily characterized by its chronic pattern and it can have important modifications in the quality of life of the patients and caretakers. One of the fastest-growing topics in translational medicine today is the exploration of new or repurposed functional biomaterials into drug delivery therapeutic applications. This area has gained a considerable amount of research which produced many innovative drug delivery systems for inflammatory skin diseases like AD. Chitosan, a polysaccharide, has attracted attention as a functional biopolymer for diverse applications, especially in pharmaceutics and medicine, and has been considered a promising candidate for AD treatment due to its antimicrobial, antioxidative, and inflammatory response modulation properties. The current pharmacological treatment for AD involves prescribing topical corticosteroid and calcineurin inhibitors. However, the adverse reactions associated with the long-term usage of these drugs such as itching, burning, or stinging sensation are also well documented. Innovative formulation strategies, including the use of micro- and nanoparticulate systems, biopolymer hydrogel composites, nanofibers, and textile fabrication are being extensively researched with an aim to produce a safe and effective delivery system for AD treatment with minimal side effects. This review outlines the recent development of various chitosan-based drug delivery systems for the treatment of AD published in the past 10 years (2012-2022). These chitosan-based delivery systems include hydrogels, films, micro-, and nanoparticulate systems as well as chitosan textile. The global patent trends on chitosan-based formulations for the AD are also discussed.

Cellulose hydrogel development from unbleached oil palm biomass pulps for dermal drug delivery.

Hydrogels are an attractive platform for drug delivery to the skin. Current cellulose hydrogel developments commonly focus on readily available bleached woody cellulose. Considering the detrimental environmental impacts of bleaching reagents, unbleached non-woody biomass was proposed as an alternative. Herein, this study aims to develop hydrogel from native cellulose extracted from oil palm empty fruit bunches for dermal drug delivery with an emphasis on evaluating the effect of alkali solvent compositions on hydrogel formation. Unbleached dissolving pulps were solubilized in alkali solvents containing sodium hydroxide (NaOH) (6-8%w/v) and urea (4-6%w/v) before crosslinking. Hydrogels were loaded with ibuprofen for skin permeation studies. Light brownish hydrogels formed are aesthetically acceptable and biodegradable with low cytotoxicity. NaOH content has a dominant role over urea where thinner and deformable crosslinked network walls in a porous hydrogel structure are associated with high NaOH content. Synergistic effects (cellulose solubility: 94 %; swelling ratio: ~2800 %) were observed at 7%w/v NaOH and 4%w/v urea with low toxicity. Most hydrogels showed >80 % of ibuprofen permeated into the skin and this increased with the swelling ratio of hydrogels. Unbleached cellulose pulps have excellent potential for hydrogel fabrication with outstanding physicomechanical properties for dermal drug delivery.

Development and Characterisation of a Topical Methyl Salicylate Patch: Effect of Solvents on Adhesion and Skin Permeation.

The advent of skin patch formulation design and technology has enabled the commercialisation of methyl salicylate (MS) as a topical patch. However, the most fundamental aspect of skin permeation is unknown at present. The study aims to investigate the effect of solvent choice on the skin permeation of MS in a neat solvent system and patch formulation with an emphasis on patch adhesion. MS in six selected solvents (propylene glycol (PG), Transcutol®, isopropyl myristate, Labrasol®, Plurol® oleique CC 497 and Maisine® CC) was characterised and in vitro permeation studies were also performed. An ATR-FTIR analysis on solvent-treated skin was conudcted. Patch formulation was prepared and characterised for adhesion, in vitro drug release and skin permeation studies. The highest MS permeation was found in neat PG over 24 h (~90 µg/cm2) due to its strong skin protein conformation effect. Transcutol® and isopropyl myristate showed better skin deposition and formulation retention, respectively. Nevertheless, PG enhanced the patch adhesion despite having a lower cumulative amount of MS permeated (~80 µg/cm2) as compared with Transcutol® and Maisine® (~110-150 µg/cm2). These two solvents, however, demonstrated better skin deposition and formulation retention but a lower patch adhesion. The unpredictable influence of the solvent on patch adhesion highlights the importance of the trade-off between patch adhesion and skin permeation during formulation design.

Dermal Delivery of Diclofenac Sodium-In Vitro and In Vivo Studies.

Previously, we reported the use of confocal Raman spectroscopy (CRS) as a novel non-invasive approach to determine drug disposition in the skin in vivo. Results obtained by CRS were found to correlate with data from the well-established in vitro permeation test (IVPT) model using human epidermis. However, these studies used simple vehicles comprising single solvents and binary or ternary solvent mixtures; to date, the utility of CRS for monitoring dermal absorption following application of complex marketed formulations has not been examined. In the present work, skin delivery of diclofenac sodium (DFNa) from two topical dermatological drug products, namely Diclac® Lipogel 10 mg/g and Primofenac® Emulsion gel 1%, was determined by IVPT and in vivo by both CRS and tape stripping (TS) methodologies under similar experimental conditions. The in vivo data were evaluated against the in vitro findings, and a direct comparison between CRS and TS was performed. Results from all methodologies showed that Diclac promoted significantly greater DFNa delivery to the skin (p < 0.05). The cumulative amounts of DFNa which permeated at 24 h in vitro for Diclac (86.5 ± 9.4 µg/cm2) were 3.6-fold greater than the corresponding amounts found for Primofenac (24.4 ± 2.7 µg/cm2). Additionally, total skin uptake of DFNa in vivo, estimated by the area under the depth profiles curves (AUC), or the signal intensity of the drug detected in the upper stratum corneum (SC) (4 µm) ranged from 3.5 to 3.6-fold greater for Diclac than for Primofenac. The shape of the distribution profiles and the depth of DFNa penetration to the SC estimated by CRS and TS were similar for the two methods. However, TS data indicated a 4.7-fold greater efficacy of Diclac relative to Primofenac, with corresponding total amounts of drug penetrated, 94.1 ± 22.6 µg and 20.2 ± 7.0 µg. The findings demonstrate that CRS is a methodology that is capable of distinguishing skin delivery of DFNa from different formulations. The results support the use of this approach for non-invasive evaluation of topical products in vivo. Future studies will examine additional formulations with more complex compositions and will use a wider range of drugs with different physicochemical properties. The non-invasive nature of CRS coupled with the ability to monitor drug permeation in real time offer significant advantages for testing and development of topical dermatological products.

Development and validation of a gradient HPLC-UV method for mitragynine following in vitro skin permeation studies.

Mitragynine is a promising candidate for pain relief and opiate replacement but the investigations for drug delivery are lacking. This study aims to investigate the potential of mitragynine to be delivered through the skin with an emphasis on developing and validating a gradient HPLC-UV analytical method to determine mitragynine in the samples collected during in vitro skin permeation studies. The optimised method involves a gradient elution using a C18 column with a mobile phase comprising acetonitrile and 0.1 %v/v of formic acid (0-1 min: 30:70 to 70:30 (v/v) and hold up to 4 min; 4-6 min: return to 30:70 (v/v) and hold up to 10 min) at a flow rate of 1.2 mL/min. This method was validated based on the standards set by the International Council on Harmonisation guidelines. The method showed mitragynine elution at âˆ¼ 4 min with adequate linearity (R2 ≥ 0.999 for concentration ranges of 0.5-10 and 10-175 µg/mL) and acceptable limits of detection and quantification at 0.47 and 1.43 µg/mL, respectively. The analytical performance is robust with excellent precision and accuracy. This method was used to evaluate the in vitro skin permeation of mitragynine (5 %w/v) from simple solvent systems over 48 hr. The results showed a cumulative amount of mitragynine permeated at âˆ¼ 11 µg/cm2 for dimethyl sulfoxide and âˆ¼ 4 µg/cm2 for propylene glycol. The study not only addressed the issues of the currently available HPLC-UV methods that limit the direct application but also affirmed the potential of mitragynine to be delivered through the skin.

Nanocrystalline cellulose isolation via acid hydrolysis from non-woody biomass: Importance of hydrolysis parameters.

The use of nanocrystalline cellulose (NCC) as a renewable and green biomaterial in diverse value-added applications has roused substantial interest. Sourcing NCCs from the abundantly available non-woody biomass becomes attractive due to its high cellulose content and low cost. Acid hydrolysis using mineral acids has been widely explored as a facile, low-cost, and efficient way of isolating NCCs. Still, the technical aspect of the extraction procedure is lacking. This review gathers the available knowledge on the NCC extraction using hydrolysis with mineral acids from non-woody biomass and provides a critical overview of the extraction parameters to be considered from the feedstocks and related pretreatment to the final hydrolysis procedure. To fulfill an operationally feasible production of NCCs, this review shares considerations and challenges on the biomass characteristics and pretreatment as well as hydrolysis parameters for optimizing NCC production and tailoring its application.

Thermal analysis of mammalian stratum corneum using differential scanning calorimetry for advancing skin research and drug delivery.

For effective topical and transdermal drug delivery, it is necessary for most actives to penetrate and permeate through the stratum corneum (SC). Extensive investigation of the thermal behaviour of mammalian SC has been performed to understand the barrier function of the skin. However, little attention has been paid to the related experimental variables in thermal analysis of the SC using differential scanning calorimetry that may influence the results obtained from such studies. In this review, we provide a comprehensive overview of the thermal transitions of the SC of both porcine and human skin. More importantly, the selection and impact of the experimental and instrumental parameters used in thermal analysis of the SC are critically evaluated. New opportunities for the use of thermal analysis of mammalian SC in advancing skin research, particularly for elucidation of the actions of excipients employed in topical and transdermal formulations on the skin are also highlighted.

Advanced structural characterisation of pharmaceuticals using nano-thermal analysis (nano-TA).

The production of drug delivery systems fabricated at the nano scale comes with the challenges of identifying reliable characterisation tools, especially for solid dosage forms. A full understanding of physicochemical properties of solid-state systems at a high spatial resolution is essential to monitor their manufacturability, processability, performance (dissolution) and stability. Nano-thermal analysis (nano-TA), a hybrid of atomic force microscopy (AFM) and thermal analysis, has emerged as a solution to address the need for complete characterisation of samples with surface heterogeneity. Nano-TA provides not only physical information using conventional AFM but also the thermal behaviour of these systems as an additional chemical dimension. In this review, the principles and techniques of nano-TA are discussed with emphasis on recent pharmaceutical applications. Building on nano-TA, the combination of this approach with infrared spectroscopic analysis is briefly introduced. The challenges and considerations for future development of nano-TA characterisation are also outlined.

Topical delivery of salicylates.

Salicylates have a long history of use for pain relief. Salicylic acid and methyl salicylate are among the widely used topical salicylates namely for keratolytic and anti-inflammatory actions, respectively. The current review summarises both passive and active strategies, including emerging technologies employed to enhance skin permeation of these two salicylate compounds. The formulation design of topical salicylic acid targets the drug retention in and on the skin based on the different indications including keratolytic, antibacterial and photoprotective actions, while the investigations of topical delivery strategies for methyl salicylate are limited. The pharmacokinetics and metabolisms of both salicylate compounds are discussed. The current overview and future perspectives of the topical delivery strategies are also highlighted for translational considerations of formulation designs.

Dermatologic reactions to disinfectant use during the COVID-19 pandemic.

Infection preventive practice of using disinfectants against SARS-CoV-2 has become the new normal due to the COVID-19 pandemic. Although disinfectants may not be applied directly to the human body, it remains at high risk of exposure including close skin contact on disinfected surfaces or during handling. This dermal contact, on a regular basis, can induce hazardous skin reactions like irritation, inflammation, and burning in severe conditions. Disinfectants are germicide chemicals that can penetrate the skin and create skin reactions that are usually regarded as irritant and allergic contact dermatitis. More importantly, disinfectants can react with skin components (proteins and lipids) to facilitate their skin penetration and disrupt the skin barrier function. Whereas the antimicrobial actions of disinfectants are well understood, much less is known regarding their dermatologic reactions, including but not limited to irritation and hypersensitivity. We reviewed the skin reactions created by those disinfectants against SARS-CoV-2 approved by the European Chemical Agency and the US Environmental Protection Agency.

Facial Skin Biophysical Profile of Women in Malaysia: Significance of Facial Skincare Product Use.

INTRODUCTION: At present, there is a lack of baseline data on the facial skin biophysical profile of women in Malaysia. The implications related to the daily habits and facial skincare product use on the skin biophysical condition are, thus, unknown. In this study, we aim to evaluate facial skin biophysical parameters of Malaysian women and examine the influence of demographic characteristics, daily habits, and facial skincare product use on these parameters. METHODS: Four skin biophysical parameters - transepidermal water loss (TEWL), melanin content, elasticity, and collagen intensity - were assessed on the cheek of the subjects (20-60 years). Demographic background, daily habits, and skincare product use were gauged through a survey. Only 197 from the 213 subjects recruited initially were used for analysis after the data were screened for normality. RESULTS: The biophysical parameters were similar in different races, except a higher melanin content in Indian female individuals. Elasticity and collagen intensity reduced with age, while melanin content increased in the older age-groups. But no difference was observed in TEWL at different ages. Evaluating the influence of daily habits, we observed that exercise significantly lowered TEWL and increased melanin content, which may be associated with UV radiation exposure. Facial skincare products are popular among the female subjects (>85% users). Products with moisturizing, sunscreening, and other skincare functions (astringent, antiaging, and anti-wrinkle) were preferred by subjects of all ages. These product functions significantly improve skin elasticity and reduce melanin content in the young adults. While aged women recognized the importance of having an additional skin-lightening function in their skincare routine. Although the influence of individual skincare function on skin biophysical parameters was mostly positive, the alteration of these parameters varied at different ages. CONCLUSION: This is the first report of facial skin biophysical profile of Malaysian women. There is no difference among 3 major races saved for melanin content. This work demonstrated age-dependent influences on the biophysical parameters, except TEWL. The significance of skincare product use is well reflected in the improvement of these parameters at different age-groups based on individual skincare functions.

Designing cellulose hydrogels from non-woody biomass.

Hydrogels are an attractive system for a myriad of applications. While most hydrogels are usually formed from synthetic materials, lignocellulosic biomass appears as a sustainable alternative for hydrogel development. The valorization of biomass, especially the non-woody biomass to meet the growing demand of the substitution of synthetics and to leverage its benefits for cellulose hydrogel fabrication is attractive. This review aims to present an overview of advances in hydrogel development from non-woody biomass, especially using native cellulose. The review will cover the overall process from cellulose depolymerization, dissolution to crosslinking reaction and the related mechanisms where known. Hydrogel design is heavily affected by the cellulose solubility, crosslinking method and the related processing conditions apart from biomass type and cellulose purity. Hence, the important parameters for rational designs of hydrogels with desired properties, particularly porosity, transparency and swelling characteristics will be discussed. Current challenges and future perspectives will also be highlighted.

Spatial resolution of drug crystallisation in the skin by X-ray micro-computed tomography.

Drug crystallisation in the skin is recognised as a significant problem in topical and transdermal drug delivery. Our recent investigations provided new evidence of drug crystallisation in the skin, however, confirming the precise location of crystals remains challenging. Of note, most approaches used have required disruption of the membrane by tape stripping, with crystal detection limited to the superficial skin layers. Hence, a non-destructive method for complete spatial resolution of crystallised drug in skin is still lacking. In this communication, we report the application of X-ray micro-computed tomography (microCT) to examine drug crystallisation in mammalian skin ex vivo. Permeation studies of a saturated solution of diclofenac sodium were conducted in porcine skin; subsequently, tissue samples were scanned using microCT to generate 2D and 3D maps. A layer of drug crystals was observed on the skin surface; microCT maps also confirmed the distribution of drug crystals up to a skin depth of 0.2 - 0.3 mm. MicroCT also allowed the identification of drug crystallisation as a distinct and confirmed event in the skin and as an extension from drug crystals formed on the skin. These preliminary results confirm the potential of microCT to study this important phenomenon in topical and transdermal drug delivery.