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.

Application of cocoa butter for formulation of fast melt tablets containing memantine hydrochloride.

INTRODUCTION: Fast melt tablets (FMTs) provide a convenient dosage form that rapidly dissolves on the tongue without the need for water. Cocoa butter serves as a suitable matrix system for FMTs formulation, facilitating rapid disintegration at body temperature. OBJECTIVES: This study aimed to formulate FMTs using cocoa butter as a base and investigate the effect of various disintegrants and superdisintegrants on their characteristics. METHODS: Cocoa butter-based FMTs were prepared via the fusion molding technique. Different disintegrants and superdisintegrants were added at varying concentrations and subjected to characterization. The optimal formulation was selected and incorporated with 10 mg memantine hydrochloride. RESULTS: The optimal FMT formulation consisted of 340 mg cocoa butter, 75 mg starch, and 75 mg crospovidone, exhibiting a hardness of 17.12 ± 0.31 N and a disintegration time of 32.67 ± 0.17 s. Furthermore, FMTs demonstrated a faster release profile compared to the commercially available product, Ebixa. SEM micrographs revealed homogenous blending of individual ingredients within the cocoa butter matrix and FT-IR analysis confirmed the chemical stability of memantine hydrochloride in the formulation. The dissolution profile of F17 suggested that the drug in FMTs released faster compared to Ebixia. Memantine hydrochloride achieved 98.07% of drug release in FMTs at 10 min. Moreover, the prepared FMTs exhibited stability for at least 6 months. CONCLUSION: The successful development of cocoa butter-based FMTs containing memantine hydrochloride highlights the potential of cocoa butter as viable alternative matrix-forming material for FMTs production. This innovative formulation offers patients a convenient alternative for medication administration.

Comparison of oven drying and freeze drying methods for the production of fast melt films containing quetiapine fumarate.

BACKGROUND: Quetiapine fumarate (QTP) is commonly prescribed for schizophrenic patient, typically available in tablet or oral suspension form, presenting challenges such as administration difficulties, fear of choking and distaste for its bitter taste. Fast melt films (FMF) offer an alternative dosage form with a simple development process, ease of administration and rapid drug absorption and action onset. OBJECTIVE: This study aims to prepare FMF with different formulations using solvent casting methods and to compare the effects of different drying methods, including oven drying and freeze drying, on the properties of the films. METHODS: Various formulations were created by manipulating polymer types (starch, hydroxypropyl methylcellulose (HPMC) and guar gum) at different concentrations, along with fixed concentrations of QTP and other excipients. Characterization tests including surface morphology, weight, thickness, pH, tensile strength, elongation length, Young's modulus, folding endurance and disintegration time were conducted. The optimal FMF formulation was identified and further evaluated for moisture and drug content, dissolution behavior, accelerated stability, X-ray diffraction (XRD), and palatability. RESULTS: FMF containing 10 mg guar gum/film developed using oven drying emerged as the optimum choice, exhibiting desirable film appearance, ultra-thin thickness (0.453 ± 0.002 mm), appropriate pH for oral intake (pH 5.0), optimal moisture content of 11.810%, rapid disintegration (52.67 ± 1.53 s), high flexibility (folding endurance > 300 times) and lower Young's modulus (1.308 ± 0.214). CONCLUSION: Oven drying method has been proven to be favorable for developing FMF containing QTP, meeting all testing criteria and providing an alternative option for QTP prescription.

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.

Insect biorefinery: A circular economy concept for biowaste conversion to value-added products.

With rapid growing world population and increasing demand for natural resources, the production of sufficient food, feed for protein and fat sources and sustainable energy presents a food insecurity challenge globally. Insect biorefinery is a concept of using insect as a tool to convert biomass waste into energy and other beneficial products with concomitant remediation of the organic components. The exploitation of insects and its bioproducts have becoming more popular in recent years. This review article presents a summary of the current trend of insect-based industry and the potential organic wastes for insect bioconversion and biorefinery. Numerous biotechnological products obtained from insect biorefinery such as biofertilizer, animal feeds, edible foods, biopolymer, bioenzymes and biodiesel are discussed in the subsequent sections. Insect biorefinery serves as a promising sustainable approach for waste management while producing valuable bioproducts feasible to achieve circular bioeconomy.

Evaluation of Aqueous Biphasic Electrophoresis System Based on Halide-Free Ionic Liquids for Direct Recovery of Keratinase.

Aqueous biphasic electrophoresis system (ABES) incorporates electric fields into the biphasic system to separate the target biomolecules from crude feedstock. Ionic liquid (IL) is regarded as an excellent candidate as the phase-forming components for ABES because of the great electrical conductivity, which can promote the electromigration of biomolecules in ABES, and thereby enhances the separation efficiency of the target biomolecules from crude feedstock. The application of electric fields to the conventional biphasic system expedites the phase settling time of the biphasic system, which eases the subsequent scaling-up steps and reduces the overall processing time of the recovery process. Alkyl sulphate-based IL is a green and economical halide-free surfactant when compared to the other halide-containing IL. The feasibility of halide-free IL-based ABES to recover Kytococcus sedentarius TWHK01 keratinase was studied. Optimum partition coefficient (Ke = 7.53 ± 0.35) and yield (YT = 80.36% ± 0.71) were recorded with IL-ABES comprised of 15.0% (w/w) [EMIM][ESO4], 20.0% (w/w) sodium carbonate and 15% (w/w) crude feedstock. Selectivity (S) of 5.75 ± 0.27 was obtained with the IL-ABES operated at operation time of 5 min with 10 V voltage supplied. Halide-free IL is proven to be a potential phase-forming component of IL-ABES for large-scale recovery of keratinase.

Recent development of unconventional aqueous biphasic system: characteristics, mechanisms and applications.

Aqueous biphasic system (ABS) is widely used in the recovery, extraction, purification and separation of proteins, enzymes, nucleic acids and antibodies. The ABS with high water content and low interfacial tension offers a biocompatible environment for the recovery of labile biomolecules. Process integration can be achieved using ABS by incorporating multiple-steps of purification, concentration and purification of biomolecules in a single-step operation which often results in high product recovery yield and purity. Conventional ABS is usually formed by aqueous solutions of two polymers or a polymer and a salt above a critical concentration. The high viscosity of polymer-based ABS causes slow phase separation and hinders the mass transfer of biomolecules, whereas polymer/salt ABS is characterized by high ionic strength resulting in the loss of bioactivity of recovered biomolecules. These limitations have encouraged the development of novel ABS which is more cost-effective for various biotechnological applications. This review discusses the characteristics and mechanisms of several types of emerging unconventional ABS using phase-forming components such as hyperbranched polymers, special salts, surfactants, magnetic fields, the addition of nanoparticles and incorporation of various solvent. Moreover, several novel applications of ABS for different separation purposes such as microfluidic-based ABS, ABS bioreactors, application of ABS as an analytical tool, and ABS micropatterning are discussed in this review. In the last section of this review, a comprehensive summary of process integration using ABS for extractive fermentations, bioconversion, crystallization and precipitation is also supplemented for the comprehensive review of various types and applications of ABS in recent years.

A Review on the Mechanisms, Applications, and Clinical Trials of Advanced Technologies in the Transdermal Drug Delivery System.

Transdermal Drug Delivery Systems (TDDS) have emerged as a promising method for administering therapeutic agents due to their non-invasive nature and patient-friendly approach. However, the effectiveness of this system is limited to drugs with specific physicochemical properties that allow for transdermal delivery as the skin acts as a barrier. To address this limitation, researchers have been exploring alternative approaches to improve drug delivery through the stratum corneum, ensuring consistent drug distribution at controlled rates. Thirdgeneration delivery systems have been developed to facilitate the delivery of various drugs across the skin barrier by disrupting the stratum corneum while protecting deeper skin tissues from injury. This review has explored various approaches that have gained popularity in enhancing drug delivery through TDDS, including microneedle-mediated, nanoparticle-enabled, thermal ablation-enhanced, and electroporation-driven delivery systems. It has discussed the mechanisms of drug delivery and potential applications for different types of drugs and detailed the clinical studies. This review has also highlighted the significant advancements in TDDS, offering valuable insights into both the pharmaceutical field and biomedical applications. The continued exploration and refinement of these delivery systems, particularly with the incorporation of Internet-of-Things (IoT) technology, Artificial Intelligence (AI), and machine learning, hold promise for expanding the scope of therapeutic interventions.

Recent Advancements in Nanopharmaceuticals for Novel Drug Delivery Systems.

Nanoparticles have found applications across diverse sectors, including agriculture, food, cosmetics, chemicals, mechanical engineering, automotive, and oil and gas industries. In the medical field, nanoparticles have garnered considerable attention due to their great surface area, high solubility, rapid dissolution, and enhanced bioavailability. Nanopharmaceuticals are specifically designed to precisely deliver drug substances to targeted tissues and cells, aiming to optimize therapeutic efficacy while minimizing potential adverse effects. Furthermore, nanopharmaceuticals offer advantages, such as expedited therapeutic onset, reduced dosages, minimized variability between fed and fasted states, and enhanced patient compliance. The increasing interest in nanopharmaceuticals research among scientists and industry stakeholders highlights their potential for various medical applications from disease management to cancer treatment. This review examines the distinctive characteristics of ideal nanoparticles for efficient drug delivery, explores the current types of nanoparticles utilized in medicine, and delves into the applications of nanopharmaceuticals, including drug and gene delivery, as well as transdermal drug administration. This review provides insights into the nanopharmaceuticals field, contributing to the development of novel drug delivery systems and enhancing the potential of nanotechnology in healthcare.

A Comprehensive Review of Challenges in Oral Drug Delivery Systems and Recent Advancements in Innovative Design Strategies.

The oral route of drug administration is often preferred by patients and healthcare providers due to its convenience, ease of use, non-invasiveness, and patient acceptance. However, traditional oral dosage forms have several limitations, including low bioavailability, limited drug loading capacity, and stability and storage issues, particularly with solutions and suspensions. Over the years, researchers have dedicated considerable effort to developing novel oral drug delivery systems to overcome these limitations. This review discusses various challenges associated with oral drug delivery systems, including biological, pharmaceutical, and physicochemical barriers. It also explores common delivery approaches, such as gastroretentive drug delivery, small intestine drug delivery, and colon-targeting drug delivery systems. Additionally, numerous strategies aimed at improving oral drug delivery efficiency are reviewed, including solid dispersion, absorption enhancers, lipidbased formulations, nanoparticles, polymer-based nanocarriers, liposomal formulations, microencapsulation, and micellar formulations. Furthermore, innovative approaches like orally disintegrating tablets (ODT), orally disintegrating films (ODF), layered tablets, micro particulates, self-nano emulsifying formulations (SNEF), and controlled release dosage forms are explored for their potential in enhancing oral drug delivery efficiency and promoting patients' compliance. Overall, this review highlights significant progress in addressing challenges in the pharmaceutical industry and clinical settings, offering novel approaches for the development of effective oral drug delivery systems.

Expression of His-tagged NADPH-dependent acetoacetyl-CoA reductase in recombinant Escherichia coli BL-21(DE3).

Poly-3-hydroxybutyrate (P(3HB)), a member of the polyhydroxyalkanoate (PHA) family, is a biodegradable polyester with diverse industrial applications. NADPH-dependent acetoacetyl-CoA reductase (phaB) is the enzyme which plays an essential role in P(3HB) synthesis by catalyzing the conversion of the intermediates. The expression of phaB enzyme using the recombinant Escherichia coli BL-21(DE3) and the purification of the synthesized enzyme were studied. The pET-B3 plasmid harbouring the phaB gene derived from Ralstonia eutropha H16, was driven by the lac promoter in E. coli BL-21(DE3). The enzyme was expressed with different induction time, temperatures and cell age. Results showed that the cell age of 4 h, induction time of 12 h at 37°C were identified as the optimal conditions for the enzyme reductase expression. A specific activity of 0.151 U mg-1 protein and total protein concentration of 0.518 mg mg-1 of dry cell weight (DCW) were attained. Affinity chromatography was performed to purify the His-tagged phaB enzyme, in which enhanced the specific activity (14.44 U mg-1) and purification fold (38-fold), despite relative low yield (44.6%) of the enzyme was obtained. The purified phaB showed an optimal enzyme activity at 30°C and pH 8.0. The findings provide an alternative for the synthesis of the reductase enzyme which can be used in the industrial-scale production of the biodegradable polymers.

Tropical Seaweeds as a Sustainable Resource Towards Circular Bioeconomy: Insights and Way Forward.

Seaweeds are photosynthetic marine macroalgae known for their rapid biomass growth and their significant contributions to global food and feed production. Seaweeds play a crucial role in mitigating various environmental issues, including greenhouse gases, ocean acidification, hypoxia, and eutrophication. Tropical seaweeds are typically found in tropical and subtropical coastal zones with warmer water temperatures and abundant sunlight. These tropical seaweeds are rich sources of proteins, vitamins, minerals, fibers, polysaccharides, and bioactive compounds, contributing to their health-promoting properties and their diverse applications across a range of industries. The productivity, cultivability, nutritional quality, and edibility of tropical seaweeds have been well-documented. This review article begins with an introduction to the growth conditions of selected tropical seaweeds. Subsequently, the multifunctional properties of tropical seaweeds including antioxidant and anti-inflammatory, anti-coagulant, anti-carcinogenic and anti-proliferative, anti-viral, therapeutic and preventive properties were comprehensively evaluated. The potential application of tropical seaweeds as functional foods and feeds, as well as their contributions to sustainable cosmetics, bioenergy, and biofertilizer production were also highlighted. This review serves as a valuable resource for researchers involved in seaweed farming as it provides current knowledge and insights into the cultivation and utilization of seaweeds.

Enhancement of protein production using synthetic brewery wastewater by Haematococcus pluvialis.

Microalgae is a sustainable protein source that has been widely applied in animal feeds, functional foods, pharmaceutical, and cosmeceutical industries. Waste products could be a potential cost-saving and nutrient-rich substrate in the cultivation of microalgae for protein production. This study aims to investigate the cultivation condition of Haematococcus pluvialis for protein synthesis using synthetic brewery wastewater (BW). H. pluvialis was cultivated in the Bold's Basal Medium (BBM) mixed with synthetic BW at different concentrations. Various cultivation conditions including brewer's spent grain hydrolysate (BSGH) concentrations, pH, and light sources were studied. The molecular weight, amino acids profile and antioxidant activity of synthesized protein were determined. Fed-batch cultivation using different percentages of fresh medium replacement for enhancing protein production was investigated. The 20% fed-batch cultivation reached 27 × 105 ± 0.42 cells/mL, and 4-fold of the protein content of 64.93 ± 5.30% of dry weight was recorded on day-13. Seven essential amino acids (lysine, threonine, histidine, phenylalanine, isoleucine, leucine, methionine) were produced in fed-batch cultivation. Red LED obtained the highest DPPH radical scavenging activity of 27.47 ± 0.98%. The findings suggested that BW is a promising substrate in the cultivation of H. pluvialis to commercially produce protein for numerous industrial applications.

Enhanced recovery of astaxanthin from recombinant Kluyveromyces marxianus with ultrasonication-assisted alcohol/salt aqueous biphasic system.

Microbial astaxanthin with strong antioxidant activity is greatly demanded for diverse applications. Extractive disruption in aqueous biphasic system (ABS) integrates the cells disruption and biomolecules recovery processes in one-step operation, allowing the direct recovery of intracellular biomolecules with biphasic system upon released from cells. In this study, astaxanthin was recovered from recombinant Kluyveromyces marxianus yeast cells via extractive disruption using alcohol/salt ABS. Recombinant K. marxianus yeast is engineered to produce high concentration of free form astaxanthin. Highest partition coefficient (K = 90.02 ± 2.25) and yield (Y = 96.80% ± 0.05) of astaxanthin were obtained with ABS composed of 20% (w/w) 1-propanol and 20% (w/w) sodium citrate of pH 5, 0.5% (w/w) yeast cells loading and additional of 1% (w/w) 1-butyl-3-methylimidazolium tetrafluoroborate (Bmim)BF4 to improve the migration of astaxanthin to alcohol-rich top phase. The incorporation of 2.5 h of ultrasonication to the biphasic system further enhanced the astaxanthin recovery in ABS. The direct recovery of astaxanthin from recombinant K. marxianus cells was demonstrated with the ultrasonication-assisted alcohol/salt ABS which integrates the extraction and concentration of astaxanthin in a single-step operation.

Characterization of alcohol/salt aqueous two-phase system for optimal separation of gallic acids.

Gallic acid (GA) is a hydrophilic polyphenol which is noteworthy for strong antioxidant capacity. The drawbacks of conventional extraction approaches such as time-consuming and high processing cost are often viewed as a hurdle to extract GA from plant sources in industrial scale. Aqueous two-phase system (ATPS) is a separation approach which can be employed as an alternative to the conventional approaches. The partition behaviour of GA in an alcohol/salt ATPS was investigated in this study to aid the development of industrial scale ATPS to extract GA from natural sources. The separation of GA was characterized by determining the types of alcohol and salt, phase composition, sample load, pH of the system and addition of adjuvants applied in the alcohol/salt ATPS construction. The hydrophilic GA was targeted to the salt-rich phase of the alcohol/salt ATPS with a partition coefficient (KGA) of 25.00 ± 0.00. The optimum condition of ATPS for the maximum partition of GA was achieved in ATPS comprised of 24% (w/w) 1-propanol and 22% (w/w) phosphate salt at pH 8 with 5% (w/w) of 1 mg/mL sample loading and 2% (w/w) NaCl addition. The findings suggest that ATPS can be applied for separation of GA from various natural sources.

Partition efficiency of cytochrome c with alcohol/salt aqueous biphasic flotation system.

Aqueous biphasic flotation (ABF) integrates aqueous biphasic system (ABS) and solvent sublation for recovery of target biomolecules. The feasibility of the alcohol/salt ABF for exclusive partition of cytochrome c to one specific phase of the system was investigated. Aliphatic alcohols of different carbon chain length (ethanol, 1-propanol and 2-propanol) and salts (sulfate, phosphate and citrate) were used for the phase formation. The effects of phase composition, concentration of sample loading, pH, flotation time and flow rate of the system on the partition efficiency of cytochrome c were determined. Cytochrome c was exclusively partitioned to the alcohol-rich top phase of the ABF of 18% (w/w) ethanol and 26% (w/w) ammonium sulfate with pH 6 and 20% (w/w) of sample loading. Highest partition coefficient (K) of 6.85 ± 0.21 and yield (YT) of 99.40% ± 0.02 were obtained with optimum flotation rate of 10 mL/min and flow rate of 10 min.

Surfactant as an Additive for the Recovery of Potent Antioxidants from Garcinia mangostana Pericarps Using a Polymer/Salt Aqueous Biphasic System.

Garcinia mangostana pericarp is a good source of natural antioxidants with numerous functional properties. The conventional approaches for the recovery of antioxidants from Garcinia mangostana pericarp require long processing time and high temperature, which may cause degradation or loss of bioactivity of antioxidants, and often result in low recovery efficiency. In this study, the extraction of antioxidants from Garcinia mangostana pericarp was investigated using a polyethylene glycol (PEG)/citrate aqueous biphasic system (ABS) with the addition of surfactants. The optimum condition for the recovery of antioxidants was achieved in PEG 1000/citrate ABS of pH 8 with tie-line length (TLL) of 48.3% (w/w), volume ratio (VR) of 1.6, 0.2% (w/w) sample loading and addition of 1.0% (w/w) Tween 85. The antioxidants were recovered in the PEG-rich top phase with a high K value of 18.23 ± 0.33 and a recovery yield of 92.01% ± 0.09. The findings suggested that the addition of surfactants to polymer/salt ABS can enhance the recovery of antioxidants from Garcinia mangostana pericarps by conserving the antioxidative properties.

Efficiency of Ionic Liquids-Based Aqueous Two-phase Electrophoresis for Partition of Cytochrome c.

Cytochrome c is a small water-soluble protein that is abundantly found in the mitochondrial intermembrane space of microorganism, plants and mammalians. Ionic liquids (ILs)-based aqueous two-phase electrophoresis system (ATPES) was introduced in this study to investigate the partition efficiency of cytochrome c to facilitate subsequent development of two-phase electrophoresis for the separation of cytochrome c from microbial fermentation. The 1-Hexyl-3-methylimidazolium bromide, (C6mim)Br and potassium citrate salt were selected as the phase-forming components. Effects of phase composition; position of electrodes; pH and addition of neutral salt on the partition efficiency of cytochrome c in the ATPES were evaluated. Highest partition coefficient (K = 179.12 ± 0.82) and yield of cytochrome c in top phase (YT = 99.63% ± 0.00) were recorded with IL/salt ATPES composed of 30% (w/w) (C6mim)Br and 20% (w/w) potassium citrate salt of pH 7 and 3.0% (w/w) NaCl addition with anode at the bottom phase and cathode at the top phase. The SDS-PAGE profile revealed that cytochrome c with a molecular weight of 12 kDa was preferably partitioned to the IL-rich top phase. Present findings suggested that the single-step ATPES is a potential separation approach for the recovery of cytochrome c from microbial fermentation. Graphical Abstract.

Recent advances on the sustainable approaches for conversion and reutilization of food wastes to valuable bioproducts.

The increasing amounts of food wastage and accumulation generated per annum due to the growing human population worldwide often associated with environmental pollution issues and scarcity of natural resources. In view of this, science community has worked towards in finding sustainable approaches to replace the common practices for food waste management. The agricultural and food processing wastes rich in nutrients are often the attractive substrates for the bioconversion for valuable bioproducts such as industrial enzymes, biofuel and bioactive compounds. The sustainable approaches on the re-utilization of food wastes as the industrial substrates for production of valuable bioproducts has meet the goals of circular bioeconomy, results in the diversify applications and increasing market demands for the bioproducts. This review discusses the current practice and recent advances on reutilization of food waste for bioconversion of valuable bioproducts from agricultural and food processing wastes.