Search Results (464)

Background: Precision medicine refers to the formulation of personalized drug regimens according to the individual characteristics of patients to achieve optimal efficacy and minimize adverse reactions. Additive manufacturing (AM), also known as three-dimensional (3D) printing, has emerged as an optimal solution for precision drug delivery, enabling customizable and the fabrication of multifunctional structures with precise control over morphology and release behavior in pharmaceutics. However, the influence of 3D printing parameters on the printed tablets, especially regarding in vitro and in vivo performance, remains poorly understood, limiting the optimization of manufacturing processes for controlled-release profiles. Objective: To establish the fabrication process of 3D-printed controlled-release tablets via comprehensively understanding the printing parameters using fused deposition modeling (FDM) combined with hot-melt extrusion (HME) technologies. HPMC-AS/HPC-EF was used as the drug delivery matrix and carbamazepine (CBZ) was used as a model drug to investigate the in vitro drug delivery performance of the printed tablets. Methodology: Thermogravimetric analysis (TGA) was employed to assess the thermal compatibility of CBZ with HPMC-AS/HPC-EF excipients up to 230 °C, surpassing typical processing temperatures (160–200 °C). The formation of stable amorphous solid dispersions (ASDs) was validated using differential scanning calorimetry (DSC), hot-stage polarized light microscopy (PLM), and powder X-ray diffraction (PXRD). A 15-group full factorial design was then used to evaluate the effects of the fan speed (20–100%), platform temperature (40–80 °C), and printing speed (20–100 mm/s) on the tablet properties. Response surface modeling (RSM) with inverse square-root transformation was applied to analyze the dissolution kinetics, specifically t_50% (time for 50% drug release) and Q_4h (drug released at 4 h). Results: TGA confirmed the thermal compatibility of CBZ with HPMC-AS/HPC-EF, enabling stable ASD formation validated by DSC, PLM, and PXRD. The full factorial design revealed that printing speed was the dominant parameter governing dissolution behavior, with high speeds accelerating release and low speeds prolonging release through porosity-modulated diffusion control. RSM quadratic models showed optimal fits for t_50% (R² = 0.9936) and Q_4h (R² = 0.9019), highlighting the predictability of release kinetics via process parameter tuning. This work demonstrates the adaptability of polymer composite AM for tailoring drug release profiles, balancing mechanical integrity, release kinetics, and manufacturing scalability to advance multifunctional 3D-printed drug delivery devices in pharmaceutics. Full article

Preservatives are essential for ensuring the stability, safety, and efficacy of pharmaceuticals, cosmetics, and food products. However, synthetic preservatives often raise toxicity concerns. This study evaluated Rosmarinus officinalis (rosemary) leaf extracts and coffee by-products from Coffea arabica and Coffea canephora as potential natural preservatives for emulsions. Antimicrobial activity was assessed against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans, along with cytotoxicity tests on human keratinocytes and antioxidant activity. The most effective extracts were incorporated into an oil-in-water emulsion for evaluation. C. arabica extracts showed the best results among coffee samples, with 43.53 mg GAE/g (gallic acid equivalents) and 2.32 mg QE/g of total phenolics (quercetin equivalents) and flavonoids, and minimum inhibitory concentrations (MICs) of 12.5 mg/mL against Escherichia coli, and 25 mg/mL against Staphylococcus aureus and Pseudomonas aeruginosa. Rosemary extract showed 158.01 ± 23.67 mg GAE/g and 1.95 ± 0.05 mg QE/g, with MICs of 2.5 mg/mL against E. coli, 1.25 mg/mL against P. aeruginosa, 0.3 mg/mL against S. aureus, and 0.08 mg/mL against Candida albicans. However, rosemary extracts displayed complete inhibition of keratinocyte growth at 20 µg/mL. A combination of both extracts had synergistic effects against S. aureus and P. aeruginosa. The emulsion met microbial safety standards in the challenge test for bacteria but not yeast. The results suggest that rosemary extracts enhance the potential of coffee by-product as a preservative system, and as a multifunctional excipient system in cosmetics, offering preservation and antioxidant protection. However, further strategies, such as adding other ingredients or adjusting the formulation pH, are required to ensure yeast inhibition. Full article

Background: The solubility and phase behavior of APIs are crucial for the development of medicines and ensuring their stability. However, conventional experimental approaches often do not allow for the precise determination of phase transitions and solubility limits, especially for poorly soluble compounds. Purpose: The aim of this study was to demonstrate the possibility of using the laser microinterferometry method, traditionally used to define the phase equilibria of polymer systems, to determine the thermodynamic solubility of the APIs. Methods: Using laser microinterferometry, the thermodynamic solubility and phase behavior of amorphous darunavir were determined in various pharmaceutical solvents, including vaseline and olive oils, water, glycerol, alcohols (methanol, ethanol, isopropanol), glycols (propylene glycol, polyethylene glycol 400, polypropylene glycol 425, polyethylene glycol 4000), and ethoxylated polyethylene glycol ether obtained from castor oil in the temperature range of 25–130 °C. Dissolution kinetics was estimated at 25 °C. Hansen solubility parameter calculations were also performed for comparison. Results: Darunavir is practically insoluble in olive and vaseline oils. In water and glycerol, an amorphous equilibrium with an upper critical solution temperature was observed, and phase diagrams were constructed for the first time. In alcohols, glycols, and ethoxylated polyethylene glycol ether obtained from castor oil, darunavir showed high solubility, accompanied by the formation of crystalline solvates. Kinetic evaluation showed that the dissolution rate of darunavir in methanol is four times faster than in ethanol and thirty times faster than in isopropanol. Comparison of the obtained data with previously published and calculated values of solubility parameters demonstrates a good correlation. Conclusions: Laser microinterferometry has been demonstrated as a potential tool for determining the thermodynamic solubility of APIs. This method allows for directly observing the dissolution process, determining the solubility limits, and detecting phase transitions. These studies are necessary for selecting appropriate excipients, preventing the formation of undesirable solvates and predicting formulation stability, which are all critical factors in early-stage drug development and pharmaceutical formulation design. Full article

The recent advancement of 3D-printed drugs is an emerging technology that has the potential for effective and safe oral delivery of personalized treatment regimens to patients, replacing the current “one size fits all” philosophy. The objective of this literature review is to highlight the importance of 3D-printing technology in the development of personalized treatments, focusing on Levetiracetam, the first FDA-approved 3D-printed drug, for the treatment of epilepsy. Levetiracetam serves as an ideal paradigm for exploring how precision medicine and 3D printing can be applied to improve treatment outcomes for other complex diseases such as diabetes, cardiovascular diseases, and cancer. 3D printing enables precise dosage and time-release profiles by modifying factors such as shape and size, and the combination of active pharmaceutical ingredients (APIs) and excipients, ensuring consistent therapeutic levels over the treatment period. Design of oral tablets with multiple compartments allows for simultaneous treatment with multiple APIs, each one with a different release profile, minimizing drug–drug interactions and side effects. This technology also supports on-demand production, making it particularly beneficial in resource-limited or urgent situations, and offers the flexibility to customize dosage forms. Additive manufacturing could be an important tool for developing personalized treatments to address the diverse medical needs of patients with complex diseases. Therefore, there is a need for more 3D-printed FDA-approved drugs in the biopharmaceutical industry to enable personalized treatment, improved patient compliance, and precise drug release control. Full article

Vitamins are chemical compounds, or a group of closely related compounds known as vitamers, which are crucial for an organism’s metabolic functions. Vitamins are categorized as either water-soluble or fat-soluble, with this second group composed of vitamins A, D, E, and K. The low aqueous solubility of these compounds often necessitates the use of pharmaceutical excipients to benefit from their medicinal efficiency. A successful example of this is the formation of the inclusion complexes with cyclodextrins (CDs), a group of cyclic oligosaccharides, composed of glucose subunits forming a macrocyclic ring. CD complexes with fat-soluble vitamins have been consistently utilized to accomplish diverse objectives, with CDs predominantly employed as solubilizers and absorption enhancers. This article examines studies detailing the synthesis and the biological, physicochemical, and structural characteristics of the inclusion complexes formed between fat-soluble vitamins and different cyclodextrins. This research demonstrates that although the fat-soluble vitamins form stable complexes with various CDs, the kind of CDs employed significantly influences the resultant properties of the complex formed. Full article

Background/Objectives: In this study, we present a green, scalable platform for the production of water-dispersible powders co-encapsulating the lipophilic bioactives curcumin (Cur) and eugenol (Eug) within the amphiphilic polymer Soluplus^® (SP) via low-temperature spray drying. Methods: The amount of Cur (1%, 5%, and 10%) and Eug (5%, 10%, 15%, and 20%) was varied to achieve single- and double-loaded water-soluble powders with the maximum amount of active substances. The powders containing a higher loading of Cur, 5% and 10% (and Eug), were obtained from water/ethanol mixtures (2:1 and 5:1 v/v ratio), while the formulation with 1% of Cur was spray-dried by using water as a solvent. Results: By leveraging aqueous or aqueous–ethanolic feed systems, we achieved high loading of the bioactive substances—up to 10% Cur and 20% Eug (w/w)—while minimizing organic solvent use. Myo-inositol was incorporated as a stabilizing excipient to modulate particle morphology, improve powder flowability, and enhance redispersibility. Physicochemical characterization revealed nanoscale micellization (53–127 nm), amorphization of both actives as confirmed by XRD and DSC, and the absence of crystalline residue. Encapsulation efficiencies exceeded 95% for Cur and 93% for Eug. Dissolution tests demonstrated a rapid release from the 5% Cur/5% Eug formulation (>85% in 5 min), while higher-loaded single-formulations showed progressively slower release (up to 45 min). Conclusions: This work demonstrates a robust and environmentally responsible encapsulation strategy, suitable for delivering poorly water-soluble phytochemicals with potential applications in oral nutraceuticals and pharmaceutical dosage forms. Full article

The development of robust and scalable tablet manufacturing methods remains a key objective in pharmaceutical technology, especially when dealing with active pharmaceutical ingredients (APIs) and excipients that exhibit suboptimal processing properties. This study evaluated two alternative manufacturing strategies for tablets containing sodium naproxen (20%, API), dolomite (65%, sustainable mineral filler), cellulose (7%), polyvinylpyrrolidone (5%, binder), and magnesium stearate (3%, lubricant). The direct compression method used a vibrating ball mill (SPEX SamplePrep 8000M), while the indirect method employed wet granulation using a pan granulator at different inclination angles. Physical properties of raw materials and granules were assessed, and final tablets were evaluated for mass, thickness, mechanical resistance, abrasiveness, and API content uniformity. Direct compression using vibratory mixing for 5–10 min (DT2, DT3) resulted in average tablet masses close to the target (0.260 g) and improved reproducibility compared to a reference V-type blender. Wet granulation produced tablets with the lowest abrasiveness (<1.0%) and minimal variability in dimensions and API content. The best uniformity (SD < 0.5%) was observed in batch IT2. Overall, vibratory mixing proved capable of achieving tablet quality comparable to that of wet granulation, while requiring fewer processing steps. This highlights its potential as an efficient and scalable alternative in solid dosage manufacturing. Full article

The efficient oral delivery of therapeutic proteins and peptides poses a tremendous challenge due to their inherent instability, large molecular size, and susceptibility to enzymatic degradation. Several nanocarrier systems, such as liposomes, solid lipid nanoparticles, and polymeric nanoparticles, have been explored to overcome these problems. Liposomes and other lipid-based nanocarriers show excellent biocompatibility and the ability to encapsulate hydrophobic and hydrophilic drugs; however, they often suffer from poor structural stability, premature leakage of the loaded drugs, and poor encapsulation efficiency for macromolecular peptides and proteins. On the other hand, polymeric nanoparticles are more stable and allow better control over drug release; nevertheless, they usually lack the necessary biocompatibility and cellular uptake efficiency. Recently, lipid-polymer hybrid nanoparticles (LPHNs) have emerged as an advanced solution combining the structural stability of polymers and the biocompatibility and surface functionalities of lipids to enhance the controlled release, stability, and bioavailability of protein and peptide drugs. In this review, an attempt was made to set a clear definition of the LPHNs and extend the concept and area, so to our knowledge, this is the first review that highlights six categories of the LPHNs based on their anatomy. Moreover, this review offers a detailed analysis of LPHN preparation methods, including conventional and nonconventional one-step and two-step processes, nanoprecipitation, microfluidic mixing, and emulsification methods. Moreover, the material attributes and critical process parameters affecting the output of the preparation methods were illustrated with supporting examples to enable researchers to select the suitable preparation method, excipients, and parameters to be manipulated to get the LPHNs with the predetermined quality. The number of reviews focusing on the formulation of peptide/protein pharmaceutics usually focus on a specific drug like insulin. To our knowledge, this is the first review that generally discusses LPHN-based delivery of biopharmaceuticals. by discussing representative examples of previous reports comparing them to a variety of nanocarrier systems to show the potentiality of the LPHNs to deliver peptides and proteins. Moreover, some ideas and suggestions were proposed by the authors to tackle some of the shortcomings highlighted in these studies. By presenting this comprehensive overview of LPHN preparation strategies and critically analyzing literature studies on this topic and pointing out their strong and weak points, this review has shown the gaps and enlightened avenues for future research. Full article

Background/Objectives: The growing interest in personalized medicine has accelerated the exploration of three-dimensional (3D) printing technologies in pharmaceutical applications. This study investigates the potential of selective laser sintering (SLS) as a flexible, small-scale manufacturing method for atomoxetine tablets tailored for individualized therapy, comparing it with conventional direct compression. Methods: Atomoxetine tablets were produced using SLS 3D printing with varying laser scanning speeds and compared to tablets made via a compaction simulator. Formulations were based on hydroxypropyl methylcellulose (HPMC) as the primary matrix former. The physical properties, drug content, disintegration time, and dissolution profiles were evaluated. The structural and chemical integrity were assessed using SEM, FTIR, DSC, and XRPD. Results: The SLS tablets exhibited comparable mechanical properties and drug content to those made by compaction. Lower laser speeds produced harder tablets with slower disintegration, while higher speeds yielded more porous tablets with ultra-rapid drug release (>85% in 15 min). All tablets met the European Pharmacopoeia dissolution criteria. No significant drug–excipient interactions or changes in crystallinity were detected. Conclusions: SLS printing is a viable alternative to traditional tablet manufacturing, offering control over drug release profiles through parameter adjustment. The technique supports the development of high-quality, patient-specific dosage forms and shows promise for broader implementation in personalized pharmaceutical therapy. Full article

Hydroxypropyl methylcellulose (Hypromellose, HPMC) is a well-known excipient used in the pharmaceutical and nutraceutical fields due to its versatile physicochemical properties. HPMC (derived from cellulose and obtained through etherification) varies in polymerization degree and viscosity, factors that both influence its functional applications. Usually, an increased polymerization degree implies a higher viscosity, depending also on the amount of polymer used. Hypromellose plays a crucial role in solid dosage forms, serving as a binder in the case of controlled-release tablets, a film-forming agent in the case of orodispersible films and mucoadhesive films, and a release modifier due to its presence in different polymerization degrees in the case of extended or modified release tablets. However, its compatibility with other excipients and the active ingredient must be carefully evaluated to prevent formulation challenges via several analytical methods such as differential scanned calorimetry (DSC), Fourier Transformed Infrared spectroscopy (FT-IR), X-Ray Particle Diffraction (XRPD), and Scanning Electron Microscopy (SEM). This review explores the physicochemical characteristics, and diverse applications of HPMC, emphasizing its significance in modern drug delivery systems. Full article

Background/Objectives: Microcrystalline cellulose (MCC) is a commonly used pharmaceutical excipient. At present, the catalytic potential of MCCs for the degradation of active pharmaceutical ingredients (APIs) has not been paid adequate attention. This study aims to investigate the representativeness of the pH value of an MCC determined in accordance with the pharmacopeia method to the acidity on its surface. Methods: We tested the differences between the catalytic activities of different MCCs and their supernatant prepared in accordance with the pharmacopeia method for the hydrolysis of ginsenoside Re, which is relatively stable in neutral or weak alkaline aqueous solutions but sensitive to acid. The sulfur content of the sulfuric acid-prepared MCC was measured using an ICP-OES. Results: All of the five tested commercially available and two self-prepared MCCs have been found to significantly promote the hydrolysis of ginsenoside Re. But their supernatants were neutral and chemically inert to Re. The sulfur content of the MCC prepared in this experiment using sulfuric acid hydrolysis was determined to be 109.60 µg/g, which is equivalent to 186 to 465 µM of sulfuric acid on the surface. Conclusions: The pH value of an MCC determined in accordance with the pharmacopeia method is not representative of the acidity on its surface. The primary reason should be that there is immobilized acid that is not so easily dissociated into the media. Ginsenoside Re is sensitive and applicable as a probe for the evaluation of the catalytic potential of pharmaceutically used MCCs. Full article

Background: Pharmaceutical compounding remains a predominantly manual process with limited innovation, particularly in non-sterile applications. This study explores the implementation of an automated compounding platform based on 3D printing to enhance precision, efficiency, and adaptability in pediatric corticosteroid formulations. Methods: Personalized hydrocortisone dosage forms were prepared in a hospital pharmacy setting using a proprietary excipient base and standardized procedures, including automated dosing and syringe heating when required. Three dosage forms—3.2 mg gel tablets, 2.8 mg water-free troches, and 1.2 mg orodispersible films (ODFs)—were selected to demonstrate the platform’s versatility and to address pediatric needs for varying strengths and dosage types. All products were prepared using a reproducible semi-solid extrusion (SSE)-based workflow with the consistent API-excipient blending and automated deposition. Results: Analytical testing confirmed that all formulations met pharmacopeial criteria for mass and content uniformity. The ODF and troche forms achieved rapid drug release, exceeding 75% within 5 min, while the gel tablet showed a slower release profile, reaching 86% by 60 min. Additionally, in-process homogeneity testing across syringe printing cycles confirmed the consistent API distribution. Conclusions: The results support the feasibility of integrating automated compounding technologies into pharmacy workflows. Such systems can improve accuracy, minimize variability, and streamline the production of customized pediatric medications, particularly for drugs with poor palatability or narrow therapeutic windows. Overall, this study highlights the potential of automation to modernize non-sterile compounding, and to better support individualized therapy. Full article

Background/Objectives: Cyclodextrins (CDs) have garnered increasing attention in pharmaceutical research due to their ability to enhance drug solubility, bioavailability, and therapeutic efficacy. Meanwhile, the gut microbiota, a key regulator of human health, has emerged as an important target in evaluating the safety and broader implications of pharmaceutical excipients. This review aims to synthesize current knowledge regarding the effects of CDs on the composition and function of the gut microbiota. Methods: A literature search following PRISMA guidelines was conducted in PubMed, ScienceDirect, and Google Scholar to identify studies on cyclodextrins and their interactions with gut microbiota. Results: Cyclodextrins, particularly α-, β-, and γ-CDs, demonstrated the capacity to modulate gut microbiota composition, promoting the growth of beneficial bacteria such as Bifidobacterium and Akkermansia. Supplementation with CDs was also associated with an increased production of short-chain fatty acids (SCFAs), which are essential for maintaining intestinal homeostasis and metabolic health. Moreover, CDs exhibited potential in lowering lipid levels and improving postprandial glycemic control without enhancing insulin secretion. Although generally recognized as safe, the toxicological profile of CDs varies depending on their type, dosage, and route of administration. Conclusions: Cyclodextrins hold considerable promise not only as pharmaceutical excipients but also as modulators of gut microbial communities, suggesting a dual therapeutic and prebiotic role. Future studies integrating metagenomic and metabolomic approaches are necessary to further elucidate the molecular mechanisms underlying CD–microbiota interactions and to optimize their application in enhancing drug delivery efficiency and promoting intestinal health. Full article

Stimuli-sensitive (in situ) drug delivery systems are a dynamically developing area of pharmaceutical research. Over the past decade, the number of studies on such systems has doubled. Among these, phase-inversion (or phase-sensitive) formulations, which were among the earliest proposed, offer significant advantages, including enhanced stability and stimuli-responsiveness. However, phase-inversion systems have remained relatively understudied. Despite the existence of three patented technologies (Atrigel^®, BEPO^®, FluidCrystal^®) for delivery systems utilizing phase inversion for various routes of administration, the absence of unified approaches to development and standardization has significantly impeded the introduction of novel, effective drugs into clinical practice. This review examined the main polymers and solvents used to create phase-inversion compositions and discussed the feasibility of introducing other excipients to modify the systems’ physicochemical properties. The most commonly used polymers included polylactide-co-glycolide, shellac, and polylactic acid. The most frequently used solvents were N-methylpyrrolidone and dimethyl sulfoxide. Following an analysis of clinical studies of phase-sensitive drugs conducted over the past 25 years, as well as original research indexed in PubMed, ScienceDirect, and Google Scholar, the main problems hindering the broader adoption of phase-inversion systems in clinical practice were identified, and recommendations for further development in this promising area were provided. Full article