Search Results (14)

Monoclonal antibodies (mAbs) are an important medical innovation in modern medicine. They are an effective therapy for several subtypes of leukaemia but may have undesirable effects, which may be minimised through the provision of interdisciplinary care including a pharmacist. The goals of this narrative review were twofold: first, to summarise the literature on the side effects of mAbs and the challenges of their preparation, and to provide recommendations for the safe preparation of mAb drug formulations for clinicians. Second, to suggest clinical roles for pharmacists to improve patient safety and clinical outcomes for leukaemia patients receiving mAb therapy. The review covers data from 178 scientific and official sources of information on the types of targeted immunobiological drugs for the treatment of various types of leukaemia. The results are a detailed description of the possible side effects from mAb therapy and a list of suggested actions that can be taken to prevent them. Pharmaceutical aspects of the use of mAbs, such as pharmacoeconomics, compounding and stability, are also discussed. The discussion is organised according to the current classification of leukaemia. The drugs considered include blinatumomab, inotuzumab ozogamicin, gemtuzumab ozogamicin, rituximab, ofatumumab, obinutuzumab, and alemtuzumab. The review offers a comprehensive resource to equip pharmacists and other clinicians to optimise mAb therapy and promote the safe use of these novel therapies. Full article

Background/Objectives: Citrus × paradisi Macfad., Rutaceae. peel is a rich source of naringin (NR), but its poor solubility and low bioavailability limit applications. This study aimed to improve NR delivery by comparing microencapsulation, liposomal microencapsulation, and buccal films containing either pure NR or grapefruit peel extract. Methods: Four spray-dried powder formulations—spray-dried NR (NS), liposomal NR (NLS), spray-dried extract (ES), and liposomal extract (ELS)—were produced using maltodextrin, β-cyclodextrin, and HPMC as wall materials. Buccal films (EP1, EP2, NP1, NP2) were prepared via solvent casting with HPMC, alginate (ALG), or polyvinyl alcohol (PVA). All samples were evaluated for solubility, moisture content, mucoadhesion, and in vitro release under simulated gastric, intestinal, and salivary conditions. Results: NR powders had the highest absolute solubility (306.42 ± 10.34 µg/mL), whereas ELS showed the lowest due to low loading. However, relative to theoretical NR content, ELS achieved the highest dissolution efficiency (55.3%), followed by NLS (42.7%), outperforming NS (5.6%) and ES (91.8%) in sustained release potential. Dual encapsulation (NLS, ELS) slowed gastric release and maintained intestinal delivery, while non-liposomal powders released rapidly. In buccal films, NP2 (NR + PVA) showed the highest release (69.97 ± 3.01 µg/mL; 40.9% efficiency) and strongest mucoadhesion (0.47 N·s). Extract-based films had lower absolute NR release but higher relative efficiency to content, likely due to co-extracted compounds enhancing wettability and matrix erosion. Conclusions: Liposomal microencapsulation improves relative dissolution efficiency and sustains intestinal release, while PVA-based buccal films enhance both release and mucoadhesion. Polymer choice and active ingredient composition are critical for optimising oral delivery of NR. These results demonstrate the potential of the proposed systems in the pharmaceutical or dietary supplement field, especially in improving the oral delivery of poorly soluble flavonoids. A graphical summary is included, visually summarising the main formulation strategies and results. Full article

Background/Objectives: Quality-by-Design (QbD) is a proactive, risk-based, regulatory-endorsed approach to the development and manufacture of medicinal products but is rarely applied to medicines compounded by pharmacists. This study aims to apply the QbD approach to optimise the compounding processes for the aqueous cream and cetomacrogol cream formulations listed in the Australian Pharmaceutical Formulary and Handbook (APF). Methods: The creams were prepared by varying the process conditions, including oil and water phase temperatures, stirring speed, cooling environment temperature, and the temperature at the end of stirring. Thirty-two samples of each cream type were prepared using combinations of processing conditions defined by a three-level factorial design. The viscosity, spreadability and creaming index of samples were assessed as response variables, and results were analysed using Stat-Ease 360© software to determine the optimal processing conditions for the two creams. To validate the predictive model and assess further cream stability, triplicate creams of each formulation were prepared using the optimised conditions and evaluated for dynamic viscosity, spreadability and creaming index. Results: Optimal conditions for aqueous cream involved heating the oil and water phases to 60 °C and 80 °C, respectively, followed by stirring the two phases at 250 rpm at 10 °C until cooling to 50 °C. For cetomacrogol cream, optimal compounding required heating the oil and water phases to 70 °C and 75 °C, respectively, with stirring the two phases at 220 rpm at ambient temperature (25 °C) until cooling to 40 °C. The conditions predicted by the models successfully yielded creams that met all specified targets. Creams compounded under optimal conditions exhibited well-defined oil droplets, with uniform droplet size in aqueous cream and mild size heterogeneity in cetomacrogol cream. Freeze-thaw testing demonstrated that both optimised creams were stable with no observable phase separation. Conclusions: This study demonstrates that a systematic experimental approach to optimising compounding parameters for the APF aqueous cream and cetomacrogol cream resulted in high-quality, stable, and reproducible products. Formulary guidelines, such as the APF, could benefit from adopting QbD approaches to improve the standardisation of compounding instructions in pharmacy practice. Full article

Additive manufacturing using fused deposition modelling (FDM) is increasingly explored for personalised drug delivery, but the lack of suitable biodegradable and printable filaments limits its pharmaceutical application. In this study, we investigated the influence of formulation and structural design on the performance of polyvinyl alcohol (PVA)-based filaments doped with theophylline anhydrous for 3D printing. To address the intrinsic brittleness and poor printability of PVA, cassava pulp-derived fibres—a sustainable and underutilised agricultural by-product—were incorporated together with polyethylene glycol (PEG 400), Eudragit^® NE 30 D, and calcium stearate. The addition of fibres modified the mechanical properties of PVA filaments through hydrogen bonding, improving flexibility but increasing surface roughness. This drawback was mitigated by Eudragit^® NE 30 D, which enhanced surface smoothness and drug distribution uniformity. The optimised composite formulation (P₁₀F₅E₅T₅) was successfully extruded and used to fabricate 3D-printed constructs. Release studies demonstrated that drug release could be modulated by pore geometry and construct thickness: wider pores enabled rapid Fickian diffusion, while narrower pores and thicker constructs shifted release kinetics toward anomalous transport governed by polymer swelling. These findings demonstrate, for the first time, the potential of cassava fibre as a functional additive in pharmaceutical FDM and provide a rational formulation–structure–performance framework for developing sustainable, geometry-tuneable drug delivery systems. Full article

Background/Objectives: This study investigates the stabilisation mechanisms of azelaic acid nanosuspensions (AZA-NS) prepared by wet media milling (WMM) using hydroxypropyl methylcellulose (HPMC) and chitosan as stabilisers. The aim was to elucidate the physical interactions relevant for stabilisation and to evaluate the effectiveness of a dual stabiliser approach to improve AZA-NS stability. Methods: AZA-NS were characterised using Fourier transform infrared spectroscopy (FTIR) to evaluate the chemical interactions, differential scanning calorimetry (DSC) for thermal properties, atomic force microscopy (AFM) to analyse the adsorption of the stabiliser on the AZA surface and X-ray diffraction (XRD) to evaluate the crystallinity. Contact angle and immersion studies were performed to evaluate wettability, and alternative stabilisers were tested for comparison. Results: Highly concentrated AZA-NS (up to 20% drug loading) were successfully produced with particle sizes between 326.8 and 541.2 nm, which are in the optimal range for follicular drug delivery. FTIR confirmed stabilisation by adsorption and not by chemical interaction. DSC revealed a melting point depression, indicating a partial disorder of the crystal lattice. AFM imaging showed different adsorption patterns for HPMC and chitosan, suggesting better surface coverage compared to alternative stabilisers. XRD confirmed the retention of the AZA crystalline form after milling. Contact angle and immersion studies showed improved wettability due to the synergistic effects of HPMC and chitosan. Alternative stabilisers showed suboptimal performance, highlighting the superior stabilising potential of the HPMC–chitosan combination. Conclusions: This study provides important insights into the dual stabilisation mechanisms and highlights the importance of combining steric and electrostatic stabilisers for the formulation of stable nanosuspensions of medium soluble drugs such as AZA. These results support the development of optimised nanosuspensions with increased stability and improved pharmaceutical applicability. Full article

Background/Objectives: Medicine acceptability is crucial for paediatric drug development, yet its assessment remains challenging due to the multifaceted nature of sensory attributes like taste, smell, and mouthfeel. Traditional methods of acceptability evaluation often involve complex questionnaires and lack standardisation, leading to difficulties in a comparative analysis across studies. This study aimed to develop a simplified, standardised approach for assessing medicine acceptability introducing the Net Promoter Score (NPS) framework to derive a Medicine Acceptability Score (MAS). Methods: A retrospective analysis was conducted using taste assessment data from nine paediatric formulations across four studies. The MAS was calculated by identifying an optimal range for categorising participant responses, which encapsulated diverse sensory attributes into a single metric. Validation was performed across various age groups and different formulations to test the reliability and discriminatory power of MAS. Results: The MAS effectively discriminated between acceptable and unacceptable formulations, providing a practical tool for formulation development. Conclusions: The MAS offers a novel, standardised metric for evaluating paediatric medicine acceptability, addressing key limitations of traditional methods. Future studies are recommended to refine the MAS model through the establishment of benchmark scores for chronic and acute medications, thereby standardising acceptability assessment of medicines across the pharmaceutical industry. Full article

It is well established that treatment regime compliance is linked to the acceptability of a pharmaceutical formulation, and hence also to therapeutic outcomes. To that end, acceptability must be assessed during the development of all pharmaceutical products and especially for those intended for paediatric patients. Although acceptability is a multifaceted concept, poor sensory characteristics often contribute to poor patient acceptability. In particular, poor taste is often cited as a major reason for many patients, especially children, to refuse to take their medicine. It is thus important to understand and, as far as possible, optimise the sensory characteristics and, in particular, the taste/flavour/mouthfeel of the formulation throughout the development of the product. Sensory analysis has been widely practiced, providing objective data concerning the sensory aspects of food and cosmetic products. In this paper, we present proposals concerning how the well-established principles of sensory analysis can best be applied to pharmaceutical product development, allowing objective, scientifically valid, sensory data to be obtained safely. We briefly discuss methodologies that may be helpful in reducing the number of samples that may need to be assessed by human volunteers. However, it is only possible to be sure whether or not the sensory characteristics of a pharmaceutical product are non-aversive to potential users by undertaking sensory assessments in human volunteers. Testing is also required during formulation assessment and to ensure that the sensory characteristics remain acceptable throughout the product shelf life. We provide a risk assessment procedure to aid developers to define where studies are low risk, the results of a survey of European regulators on their views concerning such studies, and detailed guidance concerning the types of sensory studies that can be undertaken at each phase of product development, along with guidance about the practicalities of performing such sensory studies. We hope that this guidance will also lead to the development of internationally agreed standards between industry and regulators concerning how these aspects should be measured and assessed throughout the development process and when writing and evaluating regulatory submissions. Finally, we hope that the guidance herein will help formulators as they seek to develop better medicines for all patients and, in particular, paediatric patients. Full article

Biochanin A (BCA), an isoflavone derived from various plants such as chickpea, red clover and soybean, is attracting increasing attention and is considered to have applications in the development of pharmaceuticals and nutraceuticals due to its anti-inflammatory, anti-oxidant, anti-cancer and neuroprotective properties. To design optimised and targeted BCA formulations, on one hand there is a need for more in-depth studies on the biological functions of BCA. On the other hand, further studies on the chemical conformation, metabolic composition and bioavailability of BCA need to be conducted. This review highlights the various biological functions, extraction methods, metabolism, bioavailability, and application prospects of BCA. It is hoped that this review will provide a basis for understanding the mechanism, safety and toxicity of BCA and implementing the development of BCA formulations. Full article

Cephalexin (CFX), a first-generation cephalosporin, is used to treat various infectious diseases. Although antibiotics have achieved considerable progress in the eradication of infectious diseases, their incorrect and excessive usage has contributed to various side effects, such as mouth soreness, pregnancy-related pruritus, and gastrointestinal symptoms, including nausea, epigastric discomfort, vomiting, diarrhoea, and haematuria. In addition to this, it also causes antibiotic resistance, one of the most pressing problems in the medical field. The World Health Organization (WHO) claims that cephalosporins are currently the most commonly used drugs for which bacteria have developed resistance. Hence, it is crucial to detect CFX in complex biological matrices in a highly selective and sensitive way. In view of this, a unique trimetallic dendritic nanostructure comprised of cobalt, copper, and gold was electrochemically imprinted on an electrode surface by optimising the electrodeposition variables. The dendritic sensing probe was thoroughly characterised using X-ray photoelectron spectroscopy, scanning electron microscopy, chronoamperometry, electrochemical impedance spectroscopy, and linear sweep voltammetry. The probe displayed superior analytical performance, with a linear dynamic range between 0.05 nM and 10⁵ nM, limit of detection of 0.04 ± 0.01 nM, and response time of 4.5 ± 0.2 s. The dendritic sensing probe displayed minimal response to interfering compounds, such as glucose, acetaminophen, uric acid, aspirin, ascorbic acid, chloramphenicol, and glutamine, which usually occur together in real matrices. In order to check the feasibility of the surface, analysis of a real sample was carried out using the spike and recovery approach in pharmaceutical formulations and milk samples, yielding current recoveries of 93.29–99.77% and 92.66–98.29%, respectively, with RSD < 3.5%. It only took around 30 min to imprint the surface and analyse the CFX molecule, making it a quick and efficient platform for drug analysis in clinical settings. Full article

Fibre-based oral drug delivery systems are an attractive approach to addressing low drug solubility, although clear strategies for incorporating such systems into viable dosage forms have not yet been demonstrated. The present study extends our previous work on drug-loaded sucrose microfibres produced by centrifugal melt spinning to examine systems with high drug loading and investigates their incorporation into realistic tablet formulations. Itraconazole, a model BCS Class II hydrophobic drug, was incorporated into sucrose microfibres at 10, 20, 30, and 50% w/w. Microfibres were exposed to high relative humidity conditions (25 °C/75% RH) for 30 days to deliberately induce sucrose recrystallisation and collapse of the fibrous structure into powdery particles. The collapsed particles were successfully processed into pharmaceutically acceptable tablets using a dry mixing and direct compression approach. The dissolution advantage of the fresh microfibres was maintained and even enhanced after humidity treatment for drug loadings up to 30% w/w and, importantly, retained after compression into tablets. Variations in excipient content and compression force allowed manipulation of the disintegration rate and drug content of the tablets. This then permitted control of the rate of supersaturation generation, allowing the optimisation of the formulation in terms of its dissolution profile. In conclusion, the microfibre-tablet approach has been shown to be a viable method for formulating poorly soluble BCS Class II drugs with improved dissolution performance. Full article

The aim of this work was to develop an amorphous orlistat-loaded mesoporus silica formulation using the melt-amorphisation by supercritical fluid (MA-SCF) and to investigate the effects of pressure and temperature on the pharmaceutical properties of the developed formulation. In addition, the effect of orlistat mass ratio to the mesoporus silica was also evaluated. The carbon dioxide was used as a supercritical fluid, and Neusilin^®UFL2 was selected as the mesoporous silica. For comparison with conventional amorphisation methods, orlistat formulations were also prepared by solvent evaporation and hot melt methods. Various pharmaceutical evaluations including differential scanning calorimetry, powder X-ray diffraction, scanning electron microscopy, specific surface area, total pore volume, and content uniformity were performed to characterise the prepared orlistat formulation. The melting point depression and the solubility of orlistat in supercritical carbon dioxide (SC-CO₂) were selected for the interpretation of evaluated results in relation to temperature and pressure. The total pore volume of the prepared orlistat-loaded mesoporus silica decreased with an increasing density of SC-CO₂ to about 500 g/L at a constant temperature or pressure. From these results, it was suggested that increasing the density of SC-CO₂ to about 500 g/L could result in the easier penetration of CO₂ into molten orlistat and lower viscosity, hence facilitating the introduction and loading of orlistat into the pores of Neusilin^®UFL2. However, when the density of SC-CO₂ increased to more than 500 g/L, the total pore volume increased, and this may be due to the release out of orlistat from the pores of Neusilin^®UFL2 by the increased orlistat solubility in SC-CO₂. Interestingly, as the total pore volume decreased by the filling of the drug, the drug crystallinity decreased; hence, the dissolution rate increased. Furthermore, it was shown that the most desirable mass ratio of Neusilin^®UFL2:orlistat for the amorphisation was 1:0.8 at an optimised supercritical condition of 318 K and 10 MPa. Compared with other amorphisation methods, only the sample prepared by the MA-SCF method was in pure amorphous state with the fastest dissolution rate. Therefore, it was concluded that the amorphous orlistat-loaded mesoporus silica prepared using MA-SCF under optimised conditions was more advantageous for enhancing the dissolution rate of orlistat than other conventional amorphisation methods. Full article

Amoxicillin belongs to the β-lactam family of antibiotics, a class of highly consumed pharmaceutical products used for the treatment of respiratory and urinary tract infections, and is listed as a World Health Organisation (WHO) “Essential Medicine”. The demonstrated batch enzymatic synthesis of amoxicillin is composed of a desired synthesis and two undesired hydrolysis reactions of the main substrate (6-aminopenicillanic acid (6-APA)) and amoxicillin. Dynamic simulation and optimisation can be used to establish optimal control policies to attain target product specification objectives for bioprocesses. This work performed dynamic modelling, simulation and optimisation of the batch enzymatic synthesis of amoxicillin. First, kinetic parameter regression at different operating temperatures was performed, followed by Arrhenius parameter estimation to allow for non-isothermal modelling of the reaction network. Dynamic simulations were implemented to understand the behaviour of the design space, followed by the formulation and solution of a dynamic non-isothermal optimisation problem subject to various product specification constraints. Optimal reactor temperature (control) and species concentration (state) trajectories are presented for batch enzymatic amoxicillin synthesis. Full article

The treatment of enteric bacterial infections using oral bacteriophage therapy can be challenging since the harsh acidic stomach environment renders phages inactive during transit through the gastrointestinal tract. Solid oral dosage forms allowing site-specific gastrointestinal delivery of high doses of phages, e.g., using a pH or enzymatic trigger, would be a game changer for the nascent industry trying to demonstrate the efficacy of phages, including engineered phages for gut microbiome modulation in expensive clinical trials. Spray-drying is a scalable, low-cost process for producing pharmaceutical agents in dry powder form. Encapsulation of a model Salmonella-specific phage (Myoviridae phage Felix O1) was carried out using the process of spray-drying, employing a commercially available Eudragit S100^® pH-responsive anionic copolymer composed of methyl methacrylate-co-methacrylic acid formulated with trehalose. Formulation and processing conditions were optimised to improve the survival of phages during spray-drying, and their subsequent protection upon exposure to simulated gastric acidity was demonstrated. Addition of trehalose to the formulation was shown to protect phages from elevated temperatures and desiccation encountered during spray-drying. Direct compression of spray-dried encapsulated phages into tablets was shown to significantly improve phage protection upon exposure to simulated gastric fluid. The results reported here demonstrate the significant potential of spray-dried pH-responsive formulations for oral delivery of bacteriophages targeting gastrointestinal applications. Full article

Vitamin C is widely use in cosmetics and pharmaceutics products for its active properties. However ascorbic acid shows unfavourable chemical instability such as oxidation leading to formulation problems. Therefore, carriers, such as micro- and nanoparticles, have been widely investigated as delivery systems for vitamin C to improve its beneficial effects in skin treatment. However, none of the previous studies have been able to produce microparticles with a high encapsulation entrapment of vitamin C. The aim of the present study is to use an experimental design to optimize the synthesis of polyamide microparticles for the delivery of ascorbic acid. The effect of four formulation parameters on microparticles properties (size and morphology, encapsulation efficiency and yield, release kinetics) were investigated using a surface response design. Finally, we were able to obtain stable microparticles containing more than 65% of vitamin C. This result confirms the effectiveness of using design of experiments for the optimisation of microparticle formulation and supports the proposal of using them as candidate for the delivery of vitamin C in skin treatment. Full article