Search Results (69)

Background: The development of naturally derived pharmaceutical excipients has attracted increasing interest as alternatives to conventional synthetic materials. Methods: In this study, starch–beeswax composites were prepared using native rice starch (RS) and spray-dried rice starch (SDRS) through melt levigation (ML) and emulsification (EM) techniques at starch-to-beeswax ratios of 9:1, 8:2, and 7:3. The physicochemical properties, surface hydrophobicity, morphology, tabletability, and lubrication performance of the resulting composites were evaluated and compared with magnesium stearate (MGS) and hydrogenated vegetable oil (HVO). Results: Co-processing with beeswax markedly increased the water contact angle from 35.4° and 59.7° for RS and SDRS, respectively, to values ranging from 94.5° to 125.1°, indicating successful modification of surface hydrophobicity. SEM analysis demonstrated changes in particle morphology and surface appearance following co-processing, while FT-IR confirmed the coexistence of characteristic starch- and beeswax-associated spectral features without evidence of detectable covalent modification. Co-processed formulations generally maintained or improved tabletability relative to their corresponding starch bases, with SDRS-based composites producing substantially harder tablets than RS-based formulations. The composites also reduced tablet ejection force and improved tablet mechanical properties compared with lubricant-free formulations. Among all samples, SDRS-EM-73 exhibited the best overall performance, reducing ejection force from 386.5 N for the lubricant-free control to 89.2 N, a value comparable to HVO (93.0 N), while producing tablets with high hardness (60.9 N), low friability (0.16%), and acceptable disintegration time (44.8 s). Conclusions: These findings demonstrate that co-processed starch–beeswax composites, particularly SDRS-EM-73, show considerable potential as naturally derived excipients for tablet manufacturing and may serve as sustainable alternatives to conventional tablet lubricants. Full article

The growing regulatory scrutiny and the emerging trends towards natural products and clean labels have led to a particular focus on food supplements’ composition, including excipients. The objective of this study is to establish a methodological approach combining conventional techniques, i.e., tapped density and flowability testers, with more objective and quantitative ones to identify alternative powder excipients that can replace conventional ones in the development of solid-dose formulations without affecting their processing, workability, and mechanical properties. In the first phase, the alternative powder excipients were characterized in terms of cohesiveness, compressibility, and flow function coefficient. We then evaluated the possibility of using selected excipient combinations to totally and/or partially replace the conventional excipients within three nutraceutical formulations. Glyceryl behenate at 1–3% w/w could be considered as a viable alternative lubricant to magnesium stearate without compromising the rheological properties of the mixtures. Fructo-oligosaccharides showed a free-flowing behavior comparable to calcium phosphate and microcrystalline cellulose, improving the flowability and compressibility of the formulations. The study of powder rheology could be advantageous to formulate new products or reformulate existing ones in a time- and money-saving way, leading to high-quality products that can appeal to consumers in terms of health-functional effectiveness. Full article

Background: Polyols are widely used as tablet diluents due to their high solubility, favourable taste, and ability to form robust tablets. Thus, commercially available polyols, such as mannitol and isomalt, can be considered for the preparation of low-drug-dose formulations with a high polyol load. Methods/Results: This study investigated spray-dried mannitol (Mannogem^® XL Opal SD and Pearlitol^® 200 SD) and fluid-bed granulated isomalt (galenIQ™ 720 and galenIQ™ 721) at magnesium stearate levels of 0.5 and 3.0 wt.% and consolidation pressures of 100 and 300 MPa. During the tableting of 100 consecutive tablets, materials displayed different ejection force profiles: galenIQ™ 720 and galenIQ™ 721 demonstrated low and stable ejection pressures; Mannogem^® displayed a lubricant- and compaction pressure-dependent profile, whereas Pearlitol^® produced the highest ejection forces, particularly at 0.5 wt.% magnesium stearate. To elucidate these differences, the used materials were characterised in terms of SEM imaging, moisture content, surface area and porosity analysis, particle size distribution, pXRD, and densification kinetics. Using a compaction simulator, key parameters including pressure–displacement profiles, mean yield pressure, and strain rate sensitivity of the unlubricated materials were experimentally determined, while pressure transmission, residual die-wall pressure, and friction coefficient were computed. Conclusions: The study concluded that variations in tableting properties were primarily governed by moisture content and, for mannitol grades, by manufacturing method-dependent differences in particle microstructure. These insights provide guidance for the rational selection of polyol excipients and appropriate lubrication levels in direct compression tablet formulations. Full article

This study designs stable fast-disintegrating oral granules (FDGs) of volatile liquid essential oils (cinnamon, lemon, rose, and peppermint oils) for olfactory rehabilitation. By adsorbing liquid-type essential oils onto colloidal silicon dioxide (1:1 w/w) and incorporating olive oil (1:1:0.25 w/w) as a volatile restrainer, the retention of major odorants—cinnamaldehyde, citral, phenethyl alcohol, and menthol—in cinnamon, lemon, rose, and peppermint oils, respectively, was markedly improved after 12 h of exposure at 40 °C. Then, free-flowing FDG system was formulated with sugar alcohols (mannitol, xylitol, and sorbitol), low substituted hydroxypropyl cellulose, and magnesium stearate, exhibiting rapid spreading and disintegration (<31.2 s) upon contact with aqueous media. The package of FDGs into four-layer laminated pouch afforded markedly prevent volatility of olfactory components, preserving >82% of cinnamaldehyde, citral, phenethyl alcohol, and menthol for 8 weeks under 25 °C/65% relative humidity (RH) conditions. In an in vitro volatilization test, major odorants were effectively volatilized from artificial saliva-wetted FDGs within 90 min depending on the volatility of each constituent. Therefore, this novel oral FDG system is expected to be a promising alternative for olfactory training for neurogenic smell dysfunction, providing enhanced storage stability, precise dosing, and patient compliance. Full article

Background/Objectives: Glidants and lubricants are commonly used pharmaceutical excipients that enhance powder flowability and reduce inter-particle friction, respectively, but they also negatively impact critical quality attributes such as tablet tensile strength and drug release rate. Quantifying these effects is essential as the pharmaceutical industry transitions from batch to continuous manufacturing. Methods: This study develops a rational-function-based modeling approach to capture the effects of lubricants and glidants on tableting. The framework automatically identifies upstream critical material attributes and process parameters, such as excipient concentration and mixing time, and describes their coupling to first and second orders. Reduced-order models were constructed to evaluate the influence of these variables on the four stages of powder compaction—die filling, compaction, unloading, and ejection—using formulations composed of 10% acetaminophen, microcrystalline cellulose, and varying small concentrations of magnesium stearate or colloidal silica. Tablets were fabricated across a wide range of relative densities by varying dosing position and turret speed. Results: The modeling approach successfully quantified the effects of lubricant and glidant mixing conditions on each compaction stage, providing mechanistic insight into how upstream conditions propagate through the tableting process and influence critical quality attributes. Conclusions: Overall, the rational-function-based framework offers a systematic approach to quantify and predict the impact of lubricants and glidants on tablet performance, thereby enhancing product and process understanding in continuous manufacturing. Full article

Background: Fixed-dose combinations have advanced in many therapeutic areas, including otorhinolaryngology, where hearing disorders are increasingly prevalent. Objectives: The present study focuses on developing and evaluating a new capsule combining nicergoline (NIC), piracetam (PIR), and hawthorn extract (HE) for the management of sensorineural hearing loss. Methods: The first phase methodology comprised preformulation studies (DSC, FTIR, and PXRD) to assess compatibility among active substances and excipients. Subsequently, four formulations were prepared and tested for flowability, dissolution behavior in acidic and neutral media, and stability under oxidative, thermal, and photolytic stress. Quantification of the active substances and flavonoids was performed using validated spectrophotometric and HPLC-UV methods. Results: Among the tested variants, the F1 formulation (4.5 mg NIC, 200 mg PIR, 50 mg HE, 2.5 mg magnesium stearate, 2.5 mg sodium starch glycolate, and 240.5 mg monohydrate lactose per capsule) displayed optimal technological properties, superior dissolution in acidic media, and was further selected for evaluation. The antioxidant activity of the formulation was confirmed through the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, Trolox Equivalent Antioxidant Capacity (TEAC), and iron chelation tests, and was primarily attributed to the flavonoid content of the HE. Acute toxicity tests in mice and rats indicated a high safety margin (LD₅₀ > 2500 mg/kg), while ototoxicity assessments showed no adverse effects on auditory function. Conclusions: The developed formulation displayed good stability, safety, and therapeutic potential, while the applied workflow could represent a model for the development of future fixed-dose combinations. Full article

The uniform distribution of APIs is essential in tablet formulations, particularly in direct compression, where powder blending is the only means of ensuring dose homogeneity. This study evaluated the influence of three mixing techniques—V-type mixer, planetary ball mill, and vibratory ball mill—on the physical properties and content uniformity of naproxen sodium tablets. Blends consisting of naproxen sodium, cellulose, PVP, calcium carbonate, and magnesium stearate were prepared under varied mixing intensities and characterized in terms of flowability, compressibility, and particle size distribution. The resulting tablets were analyzed for weight, thickness, hardness, friability, and API content using a simplified bypass HPLC method. The V-type mixer yielded tablets with the most consistent weight and thickness, despite the poorest blend flow properties. Vibratory milling produced the hardest tablets and best API content uniformity, although high-energy processing introduced variability at longer mixing times. The analytical method proved fast and robust, allowing for reliable API quantification without full chromatographic separation. These findings underscore the need to balance mechanical blending energy with formulation properties and support the use of streamlined analytical strategies in pharmaceutical development. Full article

Background/Objectives: Although technology has progressed and novel dosage forms have been developed, tablets are still the most used form of medication. However, the present manufacturing methods of these oral solid dosage forms offer limited capacity for personalized treatment and adaptable dosing. Personalized therapy, with a few exceptions, is not yet a part of routine clinical practice. Drug printing could be a possible approach to increase the use of personalized therapy. The aim of this work was to investigate the role of surface tension and the viscosity of inks in the formation of the printing pattern and to investigate how the porosity of substrate tablets influences the behavior of inks on the surface. Methods: Spray-dried mannitol served as a binder and filler, while magnesium stearate functioned as a lubricant in the preparation of substrate tablets. Brilliant Blue dye was a model “drug”. The ink formulation was applied to the substrates in three varying quantities. Results: Increasing the viscosity enhanced the drug content, potentially improving printing speed and pattern accuracy. However, it negatively impacted the dosing accuracy due to nozzle clogging and prolonged drying time. Viscosity had a significantly higher impact on the ink behavior than surface tension. Lowering the surface tension improved the dosing accuracy and reduced the drying time but resulted in smaller drop sizes and decreases in pattern accuracy. Reducing the substrate porosity led to longer drying times and diminished pattern accuracy. Conclusions: A target surface tension of around 30 mN/m is suggested for inkjet printing. It is necessary to further investigate the applicability of the technology with solutions of inks with high viscosity and low surface tension, including the API. 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

Objectives: This study aimed to evaluate the impact of the different hydration states of magnesium stearate (Mg.st) anhydrate (AH), monohydrate (MH), and dihydrate (DH) on the aerodynamic performance and stability of carrier-based dry powder inhalation (DPI) formulations using arformoterol and budesonide as model drugs. Methods: DPI formulations were prepared using Inhalac 251 lactose and Mg.st in various hydrated forms. The physicochemical properties of Mg.st were characterized using powder X-ray diffraction, differential scanning calorimetry, Fourier-transform infrared spectroscopy, Karl Fischer titration, dynamic vapor absorption, and Raman imaging. The aerodynamic performance was assessed employing a next-generation impactor under initial and accelerated conditions (40 °C, 75% relative humidity). Results: Mg.st-MH exhibited the highest crystallinity and the most stable moisture sorption profile, and showed the smallest particle size within the formulation as observed in the Raman images. Formulations containing Mg.st-MH demonstrated significantly higher fine particle fractions for both arformoterol (51.02 ± 5.16%) and budesonide (61.98 ± 4.09%) compared to formulations with Mg.st-AH or -DH forms. Mg.st-MH also exhibited improved performance retention under accelerated conditions, correlating with its physicochemical stability. Conclusions: The monohydrate form of magnesium stearate was the most effective force control agent, which reduced interparticulate interactions, thereby enhancing the inhalation efficiency and formulation stability. Thus, selecting an appropriate hydration form of Mg.st can improve DPI performance. Full article

Dry powder inhalers (DPI’s) are becoming increasingly popular due to growing interest in pulmonary drug delivery and their performance is the net result of a series of processes carried out during the formulation development and manufacturing process such as excipient selection, blending, milling, filling, and spray drying. To reach the small airways of the deep lung, the active pharmaceutical ingredients (API) particles need to have an aerodynamic diameter of 1–5 μm to avoid impaction and particle sedimentation in the upper respiratory tract, and due to this small particle size, the powder becomes highly cohesive resulting in poor flow. Therefore, API is usually blended with a coarse carrier to improve flowability, and due to its large size, it is more fluidizable than the micronized drug. Carrier-based DPI formulations usually consist of micronized drugs, a coarse carrier, and additional components, such as micronized lactose and force control agents, including magnesium stearate or leucine. Additionally, the manufacturing process of DPIs relies heavily on powder processing technologies, such as the micronization of API, blending, and powder filling. The aerosol performance of a DPI is significantly affected by the selection of formulation components and the processing of the formulation and, therefore, it is crucial to evaluate these parameters. This review will discuss different factors influencing the aerosol performance of carrier-based DPIs, including formulation components, device considerations, and manufacturing parameters. Additionally, novel technologies pertaining to the optimization of DPI performance are also discussed. Full article

Background/Objectives: This study aimed to establish a predictive model for critical quality attributes (CQAs) related to tablet integrity, including tablet breaking force (TBF), friability, and capping occurrence, using machine learning-based models and nondestructive experimental data. Methods: The machine learning-based models were trained on data to predict the CQAs of metformin HCl (MF)-containing tablets using a commercial-scale wet granulation process, and five models were each compared for regression and classification. We identified eight input variables associated with the process and material parameters that control the tableting outcome using feature importance analysis. Results: Among the models, the Gaussian Process regression model provided the most successful results, with R² values of 0.959 and 0.949 for TBF and friability, respectively. Capping occurrence was accurately predicted by all models, with the Boosted Trees model achieving a 97.80% accuracy. Feature importance analysis revealed that the compression force and magnesium stearate fraction were the most influential parameters in CQA prediction and are input variables that could be used in CQA prediction. Conclusions: These findings indicate that TBF, friability, and capping occurrence were successfully modeled using machine learning with a large dataset by constructing regression and classification models. Applying these models before tablet manufacturing can enhance product quality during wet granulation scale-up, particularly by preventing capping during the manufacturing process without damaging the tablets. Full article

Triclabendazole (TCB) is a well-established anthelmintic effective in treating fascioliasis, a neglected tropical disease. This study employs quality by design (QbD) to investigate the impact of TCB polymorphism and pharmacotechnical variables, from the development of immediate-release tablets to process optimization and green analysis. Critical process parameters (CPPs) and critical material attributes (CMAs), characterized by type of polymorph, composition of excipients (talc, lactose, cornstarch, and magnesium stearate), and compression force, were screened using a Plackett–Burman design (n = 24), identifying polymorphic purity and cornstarch as a CPP. To establish a mathematical model linking CPP to dissolution behaviour, a multiple linear regression (MLR) was applied to the training design (central composite design, n = 18). Simultaneously, a near-infrared spectroscopy coupled to partial least squares (NIR-PLSs) method was developed to analyze CPPs. An independent set of samples was prepared and analyzed using the NIR-PLSs model, and their dissolution profiles were also obtained. The PLSs model successfully predicted the CPPs in the new samples, yielding almost quantitative results (100 ± 3%), and MLR dissolution predictions mirrored the actual dissolution profiles (f2 = 85). In conclusion, the developed model could serve as a comprehensive tool for the development and control of pharmaceutical formulations, starting from the polymorphic composition and extending to achieve targeted dissolution outcomes. Full article

Background: Olmesartan medoxomil (OLM) is the prodrug of olmesartan, an angiotensin II type 1 receptor blocker that has antihypertensive and antioxidant activities and renal protective properties. It exhibits low water solubility, which leads to poor bioavailability and limits its clinical potential. To improve the solubility of OLM, a host–guest inclusion complex (IC) between heptakis(2,6-di-O-methyl)-β-cyclodextrin (DMβCD) and the drug substance was obtained. Along with active substances, excipients play a crucial role in the quality, safety, and efficacy of pharmaceutical formulations. Therefore, the compatibility of OLM/DMβCD IC with several pharmaceutical excipients was evaluated. Methods: IC was characterized in both solid and liquid states, employing thermoanalytical techniques, universal-attenuated total reflectance Fourier-transform infrared spectroscopy, powder X-ray diffractometry, UV spectroscopy, and saturation solubility studies. Compatibility studies were carried out using thermal and spectroscopic methods to assess potential physical and chemical interactions. Results: The 1:1 OLM:DMβCD stoichiometry ratio and the value of the apparent stability constant were determined by means of the phase solubility method that revealed an A_L-type diagram. The binary system showed different physicochemical characteristics from those of the parent entities, supporting IC formation. The geometry of the IC was thoroughly investigated using molecular modeling. Compatibility studies revealed a lack of interaction between the IC and all studied excipients at ambient conditions and the thermally induced incompatibility of IC with magnesium stearate and α-lactose monohydrate. Conclusions: The results of this study emphasize that OLM/DMβCD IC stands out as a valuable candidate for future research in the development of new pharmaceutical formulations, in which precautions should be considered in choosing magnesium stearate and α-lactose monohydrate as excipients if the manufacture stage requires temperatures above 100 °C. Full article

Background/Objectives: The aim of this work was to prepare and characterize gastroretentive floating combination tablets (GRCTs) containing 500 mg of amoxicillin trihydrate (AMX) and 125 mg of levofloxacin (LVX) that provide sustained drug release and stability at gastric pH levels for the eradication of resistant Helicobacter pylori. Method: GRCTs were prepared with low-density excipients and hydrophilic swellable polymers, including hydroxypropyl methylcellulose (HPMC) of various viscosities, polyethylene oxide (PEO), and carboxymethylcellulose (CMC), by the direct compression method. The prepared GRCTs were investigated and optimized in terms of pH stability, tablet hardness, floating lag time and total floating time, drug release rate, gel strength. Results: AMX and LVX in GRCT were stable at the HP eradication target pH above 4.0. The effervescent GRCT composition (AMX/LVX/HPMC [4000 cP]/CMC/microcrystalline cellulose/citric acid/sodium bicarbonate/calcium silicate/silicon dioxide/magnesium stearate = 500/125/50/50/125/40/60/30/10/10, w/w) yielded acceptable hardness (>6 kp), reduced floating lag time (<5 s), a long floating duration (>12 h), and sustained release rates of AMX and LVX (>90% until 12 h). This optimized GRCT had a gel strength of 107.33 ± 10.69 g and pH > 4.0, which maintained the tablets’ shape and AMX stability for 12 h. Conclusions: Collectively, the formulated effervescent GRCTs combining AMX and LVX represented a promising candidate dosage form for eradicating resistant H. pylori. Full article