Development Of Pharmaceutical Formulations Research Articles

Electrochemical Sensing Device for Carboplatin Monitoring in Proof-of-Concept Drug Delivery Nanosystems.

(1) Background: Carboplatin (CBP) is a chemotherapeutic drug widely used in the treatment of a variety of cancers. Despite its efficiency, CBP is associated with side effects that greatly limit its clinical use. To mitigate these effects, CBP can be encapsulated in targeted delivery systems, such as liposomes. Ensuring the adequate loading and release of CBP from these carriers requires strict control in pharmaceutical formulation development, demanding modern, rapid, and robust analytical methods. The aim of this study was the development of a sensor for the fast and accurate quantification of CBP and its application on proof-of-concept CBP-loaded nanosomes. (2) Methods: Screen-printed electrodes were obtained in-lab and the electrochemical behavior of CBP was tested on the obtained electrodes. (3) Results: The in-lab screen-printed electrodes demonstrated superior properties compared to commercial ones. The novel sensors demonstrated accurate detection of CBP on a dynamic range from 5 to 500 μg/mL (13.5-1350 μM). The method was successfully applied on CBP loaded and released from nanosomes, with strong correlations with a spectrophotometric method used as control. (4) Conclusions: This study demonstrates the viability of electrochemical techniques as alternative options during the initial phases of pharmaceutical formulation development.

Enhanced dissolution of curcumin-resorcinol cocrystal by the inhibition effect of HPMCAS on solution-mediated phase transformation

The present study aimed to investigate the inhibition effect of polymers on the solution-mediated phase transformation (SMPT) of cocrystals during dissolution. Curcumin-resorcinol (CUR-RES) cocrystal was prepared by slow solvent evaporation, and the best precipitation inhibitor of curcumin (CUR) was selected from five polymers including hydroxypropyl methylcellulose acetate succinate (HPMCAS), hydroxypropyl methylcellulose (HPMC) E5, HPMC E50, Poloxamer 188 (P188) and polyethylene glycol (PEG) 6000 by solvent-shift precipitation test. Then non-sink dissolution tests and intrinsic dissolution rate (IDR) tests were performed with or without HPMCAS to explore the influence of HPMCAS on the dissolution of the cocrystal. It was showed that HPMCAS could effectively inhibit the crystallization of CUR so that the dissolved drug concentration in a predissolved 0.1 % HPMCAS solution at 2 h was nearly 15 μg/mL, which was at least 150 times higher than that without HPMCAS. The red CUR-RES cocrystal turned gradually to yellow CUR during the dissolution tests in the absence of HPMCAS, while the transformation was prevented in the presence of HPMCAS. The present work fully exploits the solubility advantages of CUR-RES cocrystal via the use of precipitation inhibitor and offers important insights into reducing the risk of SMPT during cocrystal dissolution, which is crucial for the development of pharmaceutical cocrystal formulations.

Phytonano silver for cosmetic formulation- synthesis, characterization, and assessment of antimicrobial and antityrosinase potential.

Novel formulations of silver nanoparticles remain exciting if it is applicable for cosmetic purposes. This study proposes a value-added brand-new nanomaterial for improving skin complexion by inhibiting melanin development. This work aims to develop cost effective, efficient, natural silver nanoparticles phytomediated by aqueous extract of leaf sheath scales of Cocos nucifera (Cn-AgNPs) having potential as tyrosinase inhibitors hindering melanin synthesis. The formation of Cn-AgNPs was assessed spectrophotometrically and confirmed by the sharp SPR spectrum at 425nm. The chemical composition profiling was characterized by X-ray diffraction (XRD) and Fourier Transform Infrared (FTIR) spectroscopy. The morphology was confirmed by Field Emission Scanning Electron Microscopy (FESEM) and the thermal stability was assessed by Thermogravimetric analysis (TGA). Pharmacological application studies supported the materialization of Cn-AgNPs with significant antityrosinase potential and considerably improved antibacterial and antioxidant properties. Cn-AgNPs showed potential antibacterial effects against gram-positive and negative strains, including prominent infectious agents of the skin. Antioxidant capacity was confirmed with an IC50 of 57.8μg/mL by DPPH radical scavenging assay. Furthermore, in vitro melanin content determination was performed using SK-MEL cells. Cell line studies proved that Cn-AgNPs decrease the melanin content of cells. The IC50 value obtained was 84.82μg/mL. Hence Cn-AgNPs is proposed to be acting as a whitening agent through lessening cellular melanin content and as a significant inhibitor of tyrosinase activity. The antioxidant properties and antibacterial effects can contribute to skin rejuvenation and can prevent skin infections as well. This evidence proposes the development of a new nanostructured pharmaceutical and cosmetic formulation from Cocos nucifera leaf sheath scales.

Nanoscale colocalized thermal and chemical mapping of pharmaceutical powder aerosols

Inhalation of pharmaceutical aerosol formulations is widely used to treat respiratory diseases. Spatially resolved thermal characterization offers promise for better understanding drug release rates from particles; however, this has been an analytical challenge due to the small particle size (from a few micrometers down to nanometers) and the complex composition of the formulations. Here, we employ nano-thermal analysis (nanoTA) to probe the nanothermal domain of a pharmaceutical aerosol formulation containing a mixture of fluticasone propionate (FP), salmeterol xinafoate (SX), and excipient lactose, which is widely used to treat asthma and chronic obstructive pulmonary disease (COPD). Furthermore, atomic force microscopy-infrared spectroscopy (AFM-IR) and AFM force measurements are performed to provide nanochemical and nanomechanical information to complement the nanothermal data. The colocalized thermal and chemical mapping clearly reveals the surface heterogeneity of the drugs in the aerosol particles and demonstrates the contribution of the surface chemical composition to the variation in the thermal properties of the particles. We present a powerful analytical approach for in-depth characterization of thermal/chemical/morphological properties of dry powder inhaler particles at micro- and nanometer scales. This approach can be used to facilitate the comparison between generics and reference inhalation products and further the development of high-performance pharmaceutical formulations.

A Retrospective Analysis of Polymer Selection Using Solvent Casting: Formulation and DoE Optimization of the Amorphous Solid Dispersion of Amoxicillin Trihydrate by a Spray Drying Method

Background. Amoxicillin trihydrate possesses poor solubility, compressibility, and flow behavior. Amorphous solid dispersion prepared by spray drying could solve all three problems at the same time. Objective. To prepare amorphous solid dispersion after screening of polymers by solvent casting method using a spray drying method. Methods. The solvent casting method was used to screen polymers, PVP/VA S-630, PVP K30, Soluplus, PEG 4000, HPMC AS, and HPMC HP55, in 1 : 1 and 2 : 3 ratios and followed by spray drying after polymer selection. Results. The dissolution performance of the formulation improved with time. The optimum feed rate and feed concentration were found to have an impact on the flow properties and particle size of spray-dried formulations, and they were selected as independent variables in a 32 full factorial statistical design. The ANOVA and regression analysis suggest that the developed regression model has a significant overall fit to the data and can explain a substantial proportion of the variability in the dissolution at 10 minutes. The optimized batch was selected based on the decisive factors of minimum and maximum values of response variables. Overall, the optimized batch demonstrated improved characteristics in terms of percentage yield (32.81%), dissolution at 10 min (49.70%), and angle of repose at 31.42°. Conclusion. This study provides valuable insights into optimizing formulation strategies for preserving the amorphous state of drugs and contributes to the development of stable pharmaceutical formulations.

How spray drying processing and solution composition can affect the mAbs stability in reconstituted solutions for subcutaneous injections. Part II: Exploring each protein stabilizer effect

Despite extensive research in spray drying of biopharmaceuticals, identifying the optimal formulation composition and process conditions to minimize the various stresses a biopharmaceutical undergoes during this drying process. The current study extends previous research on investigating how spray drying processing and solution composition can affect the stability of monoclonal antibodies (mAbs) in reconstituted solutions for subcutaneous injections. The decoupling process stresses on a model mAb (mAb-A) compared to the effect of coupled spray-drying stresses revealed that excipients and protein concentration had a more pronounced effect on stabilizing mAb-A against shear and thermal/dehydration stresses than spray drying operating conditions. These results prompted the continuation of the study, with the aim to investigate in greater depth the effect of mAb-A concentration in the formulation designated to spray-drying and then the effect of type and the concentration of individual excipients (sugars, amino acids and surfactants). The outcomes of this investigation suggest that a general increase in the concentration of excipients, particularly surfactants, correlates with a reduction in aggregation and turbidity observed in the reconstituted spray-dried mAb-A powders. These results, contribute to the identification of a suitable composition for a spray-dried mAb-A powder that ensures robust stability of the protein in reconstituted solutions intended for subcutaneous injection. This valuable insight has important implications for advancing the development of pharmaceutical formulations with enhanced stability and efficacy.

The challenge of downstream processing of spray dried amorphous solid dispersions into minitablets designed for the paediatric population – A sustainable product development approach

Poorly water-soluble drugs present a significant challenge in the development of oral solid dosage forms (OSDs). In formulation development the appropriate use of excipients to adjust solubility, and the choice of manufacturing method and pharmaceutical processes to obtain a dosage form to meet the needs of the patient group, is crucial. Preparing an amorphous solid dispersion (ASD) is a well-established method for solubility enhancement, and spray drying (SD) a common manufacturing method. However, the poor flowability of spray dried materials poses a significant challenge for downstream processing. Promoting sustainability in OSD development involves embracing a versatile formulation design, which enables a broader spectrum of patients to use the product, as opposed to altering existing dosage forms retrospectively. The objective of the current study was to develop a formulation of spray dried indomethacin ASD suited to the production, by direct compression, of instant release paediatric minitablets. Excipients evaluated were PVP or HPMCAS in solid dispersions at the preformulation phase, and MCC and lactose as a filler in direct compression. From the studied formulations, a 3:1 ratio blend of Vivapur 200/Pharmatose 200 M (MCC/lactose) with 0.5% (w/w) magnesium stearate was found to be the most promising in tableting, and minitablets containing a 6.22% content of spray-dried ASD of indomethacin/PVP K 29–32 could be obtained with desired tablet hardness and pharmaceutical quality, complying with tests of weight variation and fast disintegration in an aqueous environment. As a case example, this study provides a good foundation for further studies in harnessing a sustainable approach to the development of pharmaceutical formulations that can appropriately serve different patient sub-populations.

Exploring the Fluconazole-Resistance Modifying Activity and Potential Mechanism of Action of Fixed Oil from Caryocar coriaceum Wittm. (Caryocaraceae) against Candida Species.

The fixed oil from the inner mesocarp of Caryocar coriaceum Wittm. is used in the Chapada do Araripe region of Brazil for the treatment of genitourinary candidiasis. This study aimed to evaluate the chemical composition, antifungal activity, reduction of fungal virulence, and the preliminary toxicity of the fixed oil from the inner mesocarp of C. coriaceum tested against three Candida yeasts. The oil was characterized by gas chromatography (GC-MS and GC-FID). Antifungal activity was assessed using the serial microdilution method. Additionally, the potential of the oil as an enhancer of fluconazole action was tested at sub-inhibitory concentrations (MIC/8). The mechanism of action of C. coriaceum fixed oil was determined by evaluating the inhibition of morphological transition in Candida spp. The chemical composition of the fixed oil of C. coriaceum comprised both unsaturated and saturated fatty acids. Oleic (61 %) and palmitic (33 %) acids were the major constituents. Regarding its anti-Candida activity, the oil inhibited the growth of C. albicans (IC50 : 371 μg/mL) and C. tropicalis (IC50 : 830 μg/mL). Furthermore, the oil reversed the antifungal resistance of C. albicans and C. tropicalis, restoring the susceptibility to fluconazole and reducing their IC50 from 12.33 μg/mL and 362 μg/mL to 0.22 μg/mL and 13.93 μg/mL, respectively. The fixed oil of C. coriaceum completely inhibited the morphological transition of C. albicans and C. tropicalis at a concentration of 512 μg/mL, but exhibited limited low antifungal potential against C. krusei. The observed antifungal activity may be attributed to the overproduction of reactive oxygen species. Additionally, the oil showed no toxic effect on the Drosophila melanogaster in vivo model. The fixed oil from the inner mesocarp of C. coriaceum emerge as a strong candidate for the development of new pharmaceutical formulations to treat infections caused by Candida spp.

CARDIOVASCULAR EFFECTS OF FREE OR COMPLEXED LINALOOL WITH Β-CYCLODEXTRIN: A FOCUS FOR ANTIHYPERTENSIVE ACTION

Investigating the cardiovascular effects of natural compounds, such as linalool, has aroused interest due to the potential impact on cardiovascular health. Linalool, a component present in several essential oils, has demonstrated promising pharmacological properties, including antihypertensive activity. However, its bioavailability and efficacy can be influenced by complexation with β-cyclodextrin, a strategy frequently used to improve the solubility and stability of bioactive substances. This study aimed to carry out a systematic review of the literature, exploring the cardiovascular effects of free linalool and linalool complexed with β-cyclodextrin. Objective: To investigate the cardiovascular effects of free linalool and linalool complexed with β-cyclodextrin, with emphasis on the antihypertensive action, through a systematic review of the literature. Methodology: The review was conducted according to PRISMA guidelines. The PubMed, Scielo and Web of Science databases were consulted, using the descriptors "linalool", "β-cyclodextrin", "cardiovascular effects", "antihypertensive" and "complexation". The inclusion criteria covered studies published in the last 10 years, focusing on in vivo experiments, clinical trials and systematic reviews. Articles unrelated to the topic, duplicate studies and those without peer review were excluded. Results: They revealed that linalool, when complexed with β-cyclodextrin, presented greater bioavailability and stability, enhancing its antihypertensive action. In vivo studies have demonstrated a significant reduction in blood pressure in hypertensive animal models. Furthermore, the complexation positively influenced the gastrointestinal absorption of linalool. These findings suggest that the complexed formulation may represent an effective approach to improving the cardiovascular effects of linalool. Conclusion: The systematic review highlights the relevance of complexing linalool to β-cyclodextrin as a strategy to enhance its antihypertensive effects. Understanding these mechanisms can contribute to the development of more effective pharmaceutical formulations in the management of hypertension, promoting advances in cardiovascular therapy.

Microwave-assisted Natural Gums for Drug Delivery Systems: Recent Progresses and Advances over Emerging Biopolymers and Technologies.

Natural polymers play a crucial role in a wide range of industries, allowing for extensive conjugation with a variety of materials and components to produce a vast multitude of products. Biomaterials have been extensively studied due to their application potential in pharmaceutical formulation development, tissue engineering, and biomedical fields. Despite this, many natural gums in their natural state have limitations in terms of microbial contamination, susceptibility, solubility, and stability. To surmount these limitations, chemical or physical modifications are made to the polymer to tailor its properties to particular applications. These polymer modifications integrate traditional elements of materials science, physics, biology, chemistry, medicine, and engineering. Microwave irradiation has become an established method for accelerating and facilitating chemical modification reactions over the past several decades. This method allows for the efficient execution of synthesis protocols by providing precise temperature and voltage control. In addition, microwave irradiation contributes to sustainable and environmentally friendly chemistry principles. This article highlights the importance of microwave-assisted natural gum modification in the production of novel dosage forms.

A Comprehensive Overview of Edible Natural Excipients and their Potential Use in Pharmaceutical Formulation Development

A Comprehensive Overview of Edible Natural Excipients and their Potential Use in Pharmaceutical Formulation Development

Validation of an HPLC-DAD Method for Quercetin Quantification in Nanoparticles.

The evaluation of the efficacy of incorporation of quercetin in nanoparticles is crucial, both for the development and quality control of pharmaceutical formulations. The validation of analytical methods for the precise quantification of quercetin is useful for the evaluation of various potential quercetin delivery systems and quercetin pharmacokinetics. This work aimed to validate a high-performance liquid chromatography with diode array detection (HPLC-DAD) method for quercetin detection and quantification in nanoparticles. Different mobile phase conditions and detection wavelengths (254 and 368 nm) were tested, and the major validation parameters were assessed (precision, accuracy, linearity, sensitivity, stability, and selectivity). The best peak resolution was obtained when quercetin was analyzed at 368 nm with a mobile phase of 1.5% acetic acid and a water/acetonitrile/methanol ratio of 55:40:5. Under these conditions, quercetin also eluted rapidly (retention time of 3.6 min). The method proved to be linear (R2 > 0.995), specific, and repeatable (variation coefficient between 2.4% and 6.7%) and presented intermediate precision (variation coefficient between 7.2% and 9.4%). The accuracy of the analysis ranged between 88.6% and 110.7%, and detection and quantification limits were 0.046 and 0.14 µg/mL, respectively. Quercetin solutions were more stable when stored at 4 °C than at room temperature or -20 °C. This validated method satisfied more parameters of bias assessment than most recent methods for quercetin determination and presented itself as more sensitive and efficient than general spectrophotometric methods. The method was successfully used for the analysis of quercetin incorporation in nanoparticles and will be evaluated in the future for its adequacy for the determination of quercetin in more complex matrices.

Development and validation of pharmaceutical oral formulation of bilayer tablet of sustained release and immediate release of gliclazide

Development and validation of pharmaceutical oral formulation of bilayer tablet of sustained release and immediate release of gliclazide

Development and evaluation of the in vitro schistosomicidal activity of solid dispersions based on 2-(-5-bromo-1-H-indole-3-yl-methylene)-N-(naphthalene-1-ylhydrazine-carbothiamide

Among all the neglected diseases, schistosomiasis is considered the second most important parasitic infection after malaria. Praziquantel is the most widely used drug for this disease, but its exclusive use may result in the development of drug-resistant schistosomiasis. To increase the control of the disease, new drugs have been developed as alternative treatments, among them 2-(-5-bromo-1-h-indole-3-yl-methylene)-N-(naphthalene-1-ylhydrazine-carbothiamide (LQIT/LT-50), which showed promising schistosomicidal activity in nonclinical studies. However, LQIT/LT-50 presents low solubility in water, resulting in reduced bioavailability. To overcome this solubility problem, the present study aimed to develop LQIT/LT-50 solid dispersions for the treatment of schistosomiasis. Solid dispersions were prepared through the solvent method using Soluplus©, polyethylene glycol (PEG) or polyvinylpyrrolidone (PVP K-30) as hydrophilic carriers. The formulations with the best results in the compatibility tests, aqueous solubility and preliminary stability studies have undergone solubility tests and physicochemical characterizations by Fourier-transform infrared spectroscopy (FTIR), x-ray diffractometry (XRD), exploratory differential calorimetry (DSC), thermogravimetry (TG) and Raman spectroscopy. Finally, the schistosomicidal activity was evaluated in vitro. The phycochemical analyzes showed that when using PVP K-30, there was an interaction between the PVP K-30 and LQIT/LT-50, proving the successful development of the solid dispersion. Furthermore, an increase in the solubility of the new system was observed (LQIT/LT-50:PVP K-30) in addition to the improvement in the in vitro shistosomidal activity at 1:4 (w/w) molar ratio (i.e., 20% drug loading) when compared to LQIT/LT-50 alone. The development of the LQIT/LT-50:PVP K-30 1:4 solid dispersion is encouraging for the future development of new pharmaceutical solid formulations, aiming the schistosomicidal treatment.

Investigation on photo-isomeric impurity of Roxadustat: Structure conformation, physicochemical characterization, interconversion feasibility and in vitro toxicological evaluation

This research article describes the comprehensive characterization and toxicological activities of a photo-isomeric impurity (PI) of an antianemic drug Roxadustat (ROX). The PI, which has the same molecular mass as that of the drug, possesses strikingly distinct structural features compared to the drug. A detailed investigation on structural as well as toxicological aspects of this impurity is warranted due to likelihood of formation of this impurity because of routine light exposure of the API, and due to alerts concerning to its carcinogenicity, mutagenicity, and teratogenicity based on in silico assessments reported in the literature. The molecular structure of the PI was confirmed by single crystal XRD providing the first evidence for the unambiguous structure determination. Complete physicochemical characterization of the impurity was carried out using powder X-ray diffraction, Fourier Transform Infrared Spectroscopy, Differential Scanning Calorimetry, and Thermogravimetric Analysis establishing phase identification and phase purity of the impurity. The feasibility of interconversion of API (ROX) to the impurity PI and vice versa was evaluated using the RP-HPLC and Triple Quadrupole LC-MS techniques for both the solution state as well as solid state. The in vitro toxicological activity of the PI was assessed through cytotoxicity assays, DNA fragmentation assays, morphological analysis, and COMET assay. These structural, synthetic and toxicological studies contribute to the overall understanding of drug stability, safety, and pharmaceutical formulation development of ROX.

Machine learning with active pharmaceutical ingredient/polymer interaction mechanism: Prediction for complex phase behaviors of pharmaceuticals and formulations

The high throughput prediction of the thermodynamic phase behavior of active pharmaceutical ingredients (APIs) with pharmaceutically relevant excipients remains a major scientific challenge in the screening of pharmaceutical formulations. In this work, a developed machine learning model efficiently predicts the solubility of APIs in polymers by learning the phase equilibrium principle and using a few molecular descriptors. Under the few-shot learning framework, thermodynamic theory (Perturbed-Chain Statistical Associating Fluid Theory, PC-SAFT) was employed for data augmentation, and computational chemistry was applied for molecular descriptors screening. The results showed that the developed machine learning model can predict the API-polymer phase diagram accurately, broaden the solubility data of APIs in polymers, and reproduce the relationship between API solubility and the interaction mechanisms between API and polymer successfully, which provided efficient guidance for the development of pharmaceutical formulations.

Phytochemical analysis and biological evaluation of Ferulago setifolia K. Koch.

Ferulago setifolia K. Koch (Apiaceae) has been the subject of this study, aiming to comprehensively determine its phenolic fingerprint and evaluate its various biological activities. The liquid chromatography-tandem mass spectrometry analysis of the 70% methanol extract of F. setifolia (FS) revealed the presence of 23 phytochemicals, among which chlorogenic acid, quinic acid, kaempferol-3-O-glucoside, and quercetin-3-O-glucoside were identified as the major phenolics in the extract. The biological screening included examinations of antioxidant, antibacterial, antiproliferative, and cytotoxic activities. The FS extract displayed moderate 2,2-diphenyl-1-picrylhydrazyl radical scavenging and ferric-reducing capacity, indicating moderate antioxidant activity. Furthermore, FS exhibited significant antiproliferative effects on cancer cells while showing low cytotoxicity on normal cells. The antibacterial activity findings revealed that FS demonstrated potent activity against Pseudomonas aeruginosa, Bacillus cereus, Staphylococcus aureus, and Escherichia coli. The findings of this study suggest that the methanolic extract of FS holds promise as a potential source of biologically active compounds. It can be utilized for the development of pharmaceutical formulations, thanks to its significant antiproliferative and antibacterial activities. Additionally, FS can serve as a valuable source of chlorogenic acid for industrial applications. © 2023 Society of Chemical Industry.

Preformulation

Each and every drug has physical and chemical properties which is consider before development of pharmaceutical formulation. Preformulation study is carried out for the newely synthesized drug.It gives the information regarding the Bioavailibility, Pharmacokinetics and Toxicity.

Etoricoxib-Cannabidiol Combo: Potential Role in Glioblastoma Treatment and Development of PLGA-Based Nanoparticles.

Glioblastoma (GBM) is the most frequently occurring primary malignant central nervous system tumor, with a poor prognosis and median survival below two years. Administration of a combination of non-steroidal anti-inflammatory drugs and natural compounds that exhibit a curative or prophylactic effect in cancer is a new approach to GBM treatment. This study aimed to investigate the synergistic antitumor activity of etoricoxib (ETO) and cannabidiol (CBD) in a GBM cell line model, and to develop poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) for these two substances. The activity of ETO+CBD was determined using the MTT test, cell-cycle distribution assay, and apoptosis analysis using two GBM cell lines, namely, T98G and U-138 MG. The PLGA-based NPs were developed using the emulsification and solvent evaporation method. Their physicochemical properties, such as shape, size, entrapment efficiency (EE%), in vitro drug release, and quality attributes, were determined using scanning electron microscopy, diffraction light scattering, high-performance liquid chromatography, infrared spectroscopy, and differential scanning calorimetry. The combination of ETO and CBD reduced the viability of cells in a dose-dependent manner and induced apoptosis in both tested GBM cell lines. The developed method allowed for the preparation of ETO+CBD-NPs with a spherical shape, mean particle size (MPS) below 400 nm, zeta potential (ZP) values from -11 to -17.4 mV, polydispersity index (PDI) values in the range from 0.029 to 0.256, and sufficient EE% of both drugs (78.43% for CBD, 10.94% for ETO). The combination of ETO and CBD is a promising adjuvant therapeutic in the treatment of GBM, and the prepared ETO+CBD-NPs exhibit a high potential for further pharmaceutical formulation development.

Spray drying robot for high-throughput combinatorial fabrication of multicomponent solid dispersions

During the development of pharmaceutical spray-dried formulations, many samples must be prepared for physico-chemical characterisation and dissolution testing by systematically varying parameters such as drug loading or the grades and ratios of excipients (polymers, surfactants, etc.). When spray drying from organic solvents in a traditional laboratory set-up, the process must be stopped after producing each sample and then re-started, which makes combinatorial exploration of the formulation design space rather time-consuming. The present work reports a new approach using a device built around a commercially available laboratory spray dryer, which enables the preparation of powder samples with systematically varying composition within a single spray drying run. The device consists of three main parts whose purpose is to achieve: i) automatic combinatorial preparation of feed mixtures from up to 9 different stock solutions; ii) removal of adhered particles from the internal glass walls of the cyclone to minimise sample cross-contamination; and iii) automatic collection of individual powder samples in sealed vials without breaking the inert atmosphere. To validate the device operation and to demonstrate its ability to produce sets of powder samples in a short time, two cases studies were conducted: a model system with ternary mixtures of coloured lactose, and a pharmaceutical co-amorphous formulation with two actives and a polymeric excipient. The case studies show that an identical set of samples can be produces by up to 8× faster compared to manual screening, while keeping sample cross-contamination at around 1%. Ultimately, this can significantly increase the throughput of data collection and analysis during powder formulation studies.