Formulation Excipients Research Articles

Glucuronidation of orally administered drugs and the value of nanocarriers in strategies for its overcome.

The gastrointestinal tract (GIT) plays a pivotal role in the absorption of orally administered drugs, with the small intestine serving as the primary site due to its extensive surface area and specialized cell types, including enterocytes and M cells. After oral administration, drugs are generally transported via the portal vein to the liver, where they undergo first-pass metabolism. This process involves various enzymatic reactions, including glucuronidation, facilitated by uridine diphosphate-glucuronosyltransferase (UGT), a major phase 2 reaction in mammalian metabolism. UGTs conjugate glucuronic acid to a wide array of endogenous and exogenous substrates, enhancing their solubility and excretion, but significantly affecting the bioavailability and therapeutic efficacy of drugs. UGT enzymes are ubiquitously distributed across tissues, prominently in the liver, but also in the GIT, kidneys, brain, and other organs where they play crucial roles in xenobiotic metabolism. Species-specific differences in UGT expression and activity impact the selection of animal models for pharmacological studies. Various experimental models - ranging from computational simulations (in silico) to laboratory experiments (in vitro) and animal studies (in vivo) - are employed throughout drug discovery and development to evaluate drug metabolism, including UGT activity. Effective strategies to counter pre-systemic metabolism are critical for improving drug bioavailability. This review explores several approaches including prodrugs, co-administration of specific molecules or use of inhibiting excipients in formulations. Strategies incorporating these excipients in nanoformulations demonstrate notable increases in drug absorption and bioavailability. This review highlights the importance of targeted delivery systems and excipient selection in overcoming metabolic barriers, aiming to optimize drug efficacy and patient outcomes.

Harnessing the potential of 2-methyl imidazolium dihydrogen phosphate as a protein stabilizer: Assessing its toxicity and impact on aggregation, structural integrity, and functional efficacy of monoclonal antibodies

The development of safe and effective biotherapeutics faces challenges due to protein aggregation. These aggregates, formed due to various stress factors, can lead to irreversible changes and increase the risk of immunogenicity and off-target binding. Ionic liquids (ILs) have recently gained significant attention due to their potential in stabilizing proteins and enzymes. In this investigation, we have assessed the thermal stability of bevacizumab (BmAb), in presence of 2-methyl imidazolium dihydrogen phosphate (2- MIDHP), both alone and in combination with other formulation excipients. SEC, DLS, FFF-MALS and AUC were used to study the protective effect of 2-MIDHP on BmAb aggregation. CD and fluorescence spectroscopy were used to evaluate the impact of 2-MIDHP on structural changes in BmAb, while SPR was used to assess the binding activity in the presence and absence of 2-MIDHP. Subsequently, a cell viability assay (MTT) was conducted to evaluate potential toxic effects of 2-MIDHP with BmAb. Overall, our findings suggested the potential of 2-MIDHP in enhancing the stability of BmAb without any negative impact on its structural and binding activity, and its compatibility with other formulation components, thus indicating its promising prospects for the development of improved biotherapeutics.

Hybrid Nanoparticle for Co-delivering Paclitaxel and Dihydroartemisinin to Exhibit Synergic Anticancer Therapeutics.

Anticancer treatment is required to provide effective and safe patient medicines. This research aided in developing and applying nanoparticles (NPs) for cancer treatment. The poor solubility of paclitaxel (PTX) restricts its therapeutic efficacy because of allergic side effects caused by formulation excipients. To overcome this, PTX was coupled with artemisinin derivatives and loaded into an NP drug delivery system to enhance its effects while addressing its low solubility. This study prepared and characterized a hybrid PLGA-lecithin NP containing dihydroartemisinin (DHA) and PTX for synergic anticancer therapy. A lyophilization study improved the stability of the NP drug formulations. Dual PTX- and DHA-loaded PLGA- and lecithin-based NPs were prepared using a single-step solvent evaporation method. The NP suspensions were lyophilized, and the types and ratios of cryoprotectants were investigated. The physicochemical properties of NPs and lyophilized cakes (Lyo-NPs) were characterized. The stability of the Lyo-NPs was investigated at 2-8°C and room conditions. The anticancer effects of the drug combination, NP suspension, and lyophilized powder were analyzed using an in vitro cytotoxicity assay and an in vivo model. The optimal PTX-DHA loaded PLGA-lecithin-NP was formulated (200 nm, PDI: 0.248 ± 0.003, Zeta potential: -33.60 ± 3.39 mV). Mannitol was selected for lyophilization. Lyo-NPs improved the stability of the NPs (1 year), wherein the physicochemical properties of the NPs were maintained (RDI was close to 1.0). An in-vitro cytotoxicity assay of PTX combined with DHA showed a synergistic anticancer effect (CI <1.0). The suppressive effects of Lyo-NPs on tumor growth in vivo were dose-dependent. While the cocktail of free drugs showed high toxicity (7.5 mg PTX-15 mg DHA/kg) in-vivo, Lyo-NPs showed no statistical differences in hematological and biochemical parameters compared to the control. Dual-drug-loaded hybrid PLGA-lecithin NP is a potential system to minimize severe side effects while enhancing antitumor efficacy, in which lyophilization is a key process to increase stability.

Effects of 2,4-dichlorophenoxyacetic acid (2,4-D), isolated and in a formulated product, on the functional parameters of isolated rat liver mitochondria

2,4-Dichlorophenoxyacetic acid (2,4-D) is a widely used herbicide with known implications for environmental and biological systems. Previous studies indicate its potential to interact with cellular structures, potentially impacting cellular energy and metabolism. This study aimed to investigate the toxicological effects of this molecule on isolated rat liver mitochondria, evaluating both isolated and formulated 2,4-D to comprehend the differential impacts on mitochondrial function. Our investigations did not reveal significant induction of oxidative stress, mitochondrial swelling or impacts on mitochondrial respiration; however, exposure to both forms of 2,4-D affected mitochondrial membrane integrity and function in a concentration-dependent manner, notably impacting mitochondrial ATP levels and membrane potential. Comparatively, the formulated product showed toxicity at lower concentrations regarding interaction with membranes and ATP levels (from 0.4 μM on) and isolated 2,4-D showed toxicity at lower concentrations regarding membrane potential dissipation (from 10 μM on). Notably, the effects on ATP levels and membrane fluidity suggest interactions within the mitochondrial lipid bilayer. The findings highlight that excipients in the commercial formulation of 2,4-D potentially alter its effects, underlining the importance of evaluating not only active ingredients but also formulations.

Azelaic acid-based lyotropic liquid crystals gel for acne vulgaris: Formulation optimization, antimicrobial activity and dermatopharmacokinetic study

The proposed study aimed to develop a topical gel containing azelaic acid (AZA)-based lyotropic liquid crystals (LLCs) for the treatment of acne vulgaris. AZA-based LLCs were optimized by varying Poloxamer-407 and polyvinyl alcohol concentration using a central composite design, which showed that both independent variables had a significant effect on the formulation. The highest desirable trial of AZA-based LLCs (Batch-7) containing 300 mg poloxamer-407 and 100 mg polyvinyl alcohol depicted the particle size, zeta potential, and entrapment efficiency of 184.2 nm, −16.1 mV, and 79.96 %, respectively. TEM images confirmed the globular vesicles of LLCs, and ATR-FTIR and DSC results confirmed the compatibility of formulation excipients. In vitro, the release of AZA, AZA-based LLCs, AZA-based LLC gel, and marketed gel showed a release of 23.29, 95.24, 91.07 and 59.88 %, respectively, after 24 h in phosphate buffer pH 6.8. Ex vivo release of AZA-based LLC gel displayed an 86.56 % release after 24 h. The antimicrobial activity of AZA-based LLC gel exhibited a comparable efficacy with marketed gel against Cutibacterium acnes, Staphylococcus epidermis and Staphylococcus aureus. The acute dermal irritation study indicated excellent safety and skin compatibility of AZA-based LLC gel without any erythema and edema. The dermatopharmacokinetic study displayed an enhanced drug retention for AZA-based LLC gel (146.121 ± 21.13 µg/cm2) than marketed gel (58.58 ± 15.95 µg/cm2) in the dermal layer, which would improve its therapeutic effect. These outcomes proved that AZA-based LLC gel has the potential to enhance skin penetration and retention for effective management of acne vulgaris.

Formulation and Evaluation of Paracetamol Tablet Using Konjac Glucomannan as Natural Halal Binder

Introduction: Discovery and development of novel halal excipients in tablet formulation have led to continuous interest in drug delivery research. In this study, Konjac Glucomannan, a polysaccharide derived from the tuber of Amorphophallus konjac, was used as a halal binder in the formulation of paracetamol tablets. Objective: This study aims to formulate and evaluate paracetamol tablets using konjac glucomannan as a halal binder. Methodology: Paracetamol tablets were formulated with different concentrations (5%, 10%, 15%, 20%) of KGM using the wet granulation method. The formulated paracetamol granules and tablets were subjected to different quality control tests. Results: All four formulation granules passed the pre-compression test, indicating good to passable powder flowability. The weight variation, hardness, thickness, and disintegration test results for all four formulations were within the USP limit except for the friability test. Only tablets with 20% KGM passed the test. Conclusion: 20% KGM shows good tablet binding properties compared to 5%, 10%, and 15% KGM. Hence, paracetamol tablets formulated with higher KGM as a binder produce paracetamol tablets with good physical and mechanical properties.

Evaluation of the Potential of Novel Co-Processed Excipients to Enable Direct Compression and Modified Release of Ibuprofen.

Background/Objectives: Improving the production rates of modern tablet presses places ever greater demands on the performance of excipients. Although co-processing has emerged as a promising solution, there is still a lack of directly compressible excipients for modified-release formulations. The aim of the present study was to address this issue by investigating the potential of novel co-processed excipients for the manufacture of modified-release tablets containing ibuprofen. Methods: The excipients were prepared by melt granulation of lactose monohydrate with glyceryl palmitostearate as a binder. The influence of glyceryl palmitostearate particle size, ibuprofen content, compression pressure, and compression speed on the compaction behavior of the tablet blends was analyzed. Results: Novel co-processed excipients ensured good flowability and acceptable mechanical properties of the tablets containing up to 70% ibuprofen. Furthermore, lipid-based co-processed excipients proved to be very promising for directly compressible formulations with high-dose, highly adhesive active pharmaceutical ingredients such as ibuprofen, as they do not require additional lubricants. The influence of compression speed on the tensile strength of the tablets prepared was not pronounced, indicating the robustness of these directly compressible excipients. The investigated lipid-based excipients enabled a prolonged release of ibuprofen over 10 h. Conclusions: The novel lipid-based co-processed excipients have shown great potential for directly compressible formulations with modified release of high-dose, challenging active pharmaceutical ingredients.

Multidomain Protein-Urea Interactions: Differences in Binding Behavior Lead to Different Destabilization Tendencies for Monoclonal Antibodies.

We study the influence of urea on the stability of monoclonal antibodies (mAbs) using molecular dynamics (MD) simulations in combination with differential scanning fluorimetry (DSF). We show that a denaturing cosolute such as urea binds strongly to the protein, which can lead to denaturation and enhanced aggregation behavior at high temperatures. The interaction between protein and urea crucially depends on the surface properties of the individual mAb domains and therefore affects the general binding to the protein differently. The study of these mechanisms for proteins with multiple domains, such as mAbs, encounters significant limitations in experimental analysis methods due to their complexity. Using computational and experimental methods, we are able to separate the protein-urea interaction by domain and show that Lennard-Jones interactions are mainly responsible for significant binding effects. Our results emphasize the potential of MD simulations in combination with Kirkwood-Buff theory to study the interactions between proteins with multiple domains and cosolutes as formulation excipients for drug discovery and development.

Effect of Liquid Load Level and Binder Type on the Tabletability of Mesoporous Silica Based Liquisolids

Mesoporous silica offers an easy way to transform liquids into solids, due to their high loading capacity for liquid or dissolved active ingredients and the resulting enhanced dissolution properties. However, the compression of both unloaded and loaded mesoporous silica bulk material into tablets is challenging, due to poor/non-existing binding capacity. This becomes critical when high drug loads are to be achieved and the fraction of additional excipients in the final tablet formulation needs to be kept at a minimum. Our study aimed to investigate the mechanism of compression and tabletability dependent on the Liquid Load Level of the silica and type of filler/binder in binary tabletting mixtures. To this end, Vivapur® 101, FlowLac® 90, Pearlitol® 200 SD and tricalcium citrate tetrahydrate were selected and mixed with Syloid® XDP 3050 at various Liquid Load Levels. Compaction characteristics were analysed using the StylOne® Classic 105 ML compaction simulator. Additionally, the Overall Liquid Load (OLL) was defined as a new critical quality attribute for liquisolid tablets. The Overall Liquid Load allows straightforward, formulation-relevant comparisons between various fillers/binders, liquid components, and silica types. Results indicate strong binding capacity and high plasticity of the fillers/binders as key components for successful high liquid load silica tablet formulation. A volumetric combination of 30% Vivapur® 101 and 70% 0.75 mL/g loaded Syloid® XDP 3050 proved to be the most effective mixture, achieving an Overall Liquid Load of 36–41% [v/v] and maintaining a tensile strength of 1.5 N/mm2 with various liquid vehicles.Graphical

Molecular Dynamics Simulations Reveal How Competing Protein-Surface Interactions for Glycine, Citrate, and Water Modulate Stability in Antibody Fragment Formulations.

The design of stable formulations remains a major challenge for protein therapeutics, particularly the need to minimize aggregation. Experimental formulation screens are typically based on thermal transition midpoints (Tm), and forced degradation studies at elevated temperatures. Both approaches give limited predictions of long-term storage stability, particularly at low temperatures. Better understanding of the mechanisms of action for formulation of excipients and buffers could lead to improved strategies for formulation design. Here, we identified a complex impact of glycine concentration on the experimentally determined stability of an antibody Fab fragment and then used molecular dynamics simulations to reveal mechanisms that underpin these complex behaviors. Tm values increased monotonically with glycine concentration, but associated ΔSvh measurements revealed more complex changes in the native ensemble dynamics, which reached a maximum at 30 mg/mL. The aggregation kinetics at 65 °C were similar at 0 and 20 mg/mL glycine, but then significantly slower at 50 mg/mL. These complex behaviors indicated changes in the dominant stabilizing mechanisms as the glycine concentration was increased. MD revealed a complex balance of glycine self-interaction, and differentially preferred interactions of glycine with the Fab as it displaced hydration-shell water, and surface-bound water and citrate buffer molecules. As a result, glycine binding to the Fab surface had different effects at different concentrations, and led from preferential interactions at low concentrations to preferential exclusion at higher concentrations. During preferential interaction, glycine displaced water from the Fab hydration shell, and a small number of water and citrate molecules from the Fab surface, which reduced the protein dynamics as measured by root-mean-square fluctuation (RMSF) on the short time scales of MD. By contrast, the native ensemble dynamics increased according to ΔSvh, suggesting increased conformational changes on longer time scales. The aggregation kinetics did not change at low glycine concentrations, and so the opposing dynamics effects either canceled out or were not directly relevant to aggregation. During preferential exclusion at higher glycine concentrations, glycine could only bind to the Fab surface through the displacement of citrate buffer molecules already favorably bound on the Fab surface. Displacement of citrate increased the flexibility (RMSF) of the Fab, as glycine formed fewer bridging hydrogen bonds to the Fab surface. Overall, the slowing of aggregation kinetics coincided with reduced flexibility in the Fab ensemble at the very highest glycine concentrations, as determined by both RMSF and ΔSvh, and occurred at a point where glycine binding displaced neither water nor citrate. These final interactions with the Fab surface were driven by mass action and were the least favorable, leading to a macromolecular crowding effect under the regime of preferential exclusion that stabilized the dynamics of Fab.

Denaturants and Solutol® HS15 in ophthalmic formulations: Insights into their combined effects

In the field of ophthalmology, significant attention is dedicated to developing micellar carriers to enhance ocular drug delivery. Urea is a well-known denaturant and has been used as an excipient in several ocular formulations due to its efficacy as an ocular hypotensive agent. The presence of urea as an excipient may influence the characteristics of the micellar nanocarrier in the formulation and needs to be investigated. Solutol® HS15, a well-known nonionic surfactant and a commonly used nanocarrier in drug formulations, enhances the solubilization and stability of ocular drugs. However, a detailed study of its interaction with various pharmaceutical excipients is still lacking. With this intention, the present study focuses on comprehending the interaction between Solutol® HS15 micelles with urea and its derivatives. Here, we present a detailed analysis on the influence of urea and its derivatives (methylurea, dimethylurea) on Solutol® HS15 using small-angle neutron scattering (SANS), dynamic light scattering (DLS), and cloud point (CP) measurements. The presence of urea and its derivatives strongly affects the CP, leading to a significant increase in its values when urea derivatives are present. Additionally, the SANS and DLS results also indicate a significant decrease in micellar size, suggesting demicellization. The observed effects of urea derivatives on Solutol® HS15 micelles underscore the importance of considering solvent-surfactant interactions in understanding the behavior of surfactant-based systems. This research will provide greater insight into the interactions between urea and its derivatives and Solutol® HS15, which will assist in understanding the morphology and size distribution of surfactant micelles for drug delivery applications.

Evaluation of different techniques for wet granulation and pelletization processes using milk as innovative pharmaceutical excipient for pediatric use

The present study focused on the use of milk as a novel excipient for the manufacture of pharmaceutical dosage forms specifically designed for the pediatric population. Dairy milks with different fat contents were studied to deliver paracetamol orally. The World Health Organization included milk in the list of GRAS (generally recognized as safe) substances, which together with its taste-masking ability and solubility solving properties, makes it a good candidate as an excipient in formulations containing paracetamol for pediatrics. The influence of the fat content in the milk, the fraction of paracetamol, the type of diluent and drying temperature (considered independent variables) were systematically investigated using a Design of Experiments (DoE) approach for the preparation of granules for oral administration, by wet agglomeration using different processing techniques, enabled the construction of mathematical models reflecting the correlation between the variables. Four different techniques were evaluated: wet granulation by low shear mixer, wet granulation by high shear mixer, wet granulation by fluidized bed, and extrusion and spheronization. The granules and pellets obtained were characterized for size, and size distribution of agglomerates, and complete release of the drug (dependent variables), according to the European Pharmacopoeia. The fraction of fat content in the milk promoted an increase on the dissolution rate of paracetamol. The key finding of the first two process techniques was a migration of paracetamol from powdered agglomerates towards the larger particles, probably due to friction and attrition events, which created a fraction of smaller size granules due to the fragmentation and loss of powder from the larger granules. The study has confirmed the potential of milk to be a novel and efficient excipient that can be used as a liquid binder in various agglomeration techniques to deliver drugs orally.

Harnessing spectrophotometry resolution power for determining ternary mixture for respiratory disorders treatment in their pharmaceutical formulation.

A ternary mixture incorporating Hydroxyzine hydrochloride (HYX), Ephedrine hydrochloride (EPH) and Theophylline (THP) frequently prescribed for the treatment of respiratory diseases. Herein, two spectrophotometric methods are designated and applied to resolve these three components in their mixture. Method A is ratio-subtraction combined with derivative spectrophotometry, where THP can be determined directly at its λmax 271 nm (neither HYX or EPH interfere), then for determination of HYX and EPH, the ternary mixture was divided by 22 μg/mL of THP and after subtraction of the plateau region, HYX can be determined directly at its λmax 234.2 nm (absence of EPH intervention). Finally, the third derivative (3D) spectrophotometric approach was utilized to estimate EPH by detecting the peak amplitude at 222 nm with Δλ = 4 and a scaling factor 100. Principal Component Regression (PCR) and Partial Least Squares (PLS), two multivariate calibration approaches, were applied effectively in Method B. This method effectively quantified the mixture under investigation by using the absorption spectra obtained from suitable solutions of the three components in the 210-230 nm region. The calibration models were evaluated using cross-validation with PCR and PLS, producing statistical characteristics that demonstrate the effectiveness of the calibration models. Synthetic and pharmaceutical preparations were also used to conduct external validation. In pharmaceutical formulation, these methods were successfully applied to analyze HYX, EPH, and THP without overlap from formulation's excipients. Moreover, the study's findings were statistically contrasted with those of earlier reported HPLC method. Appraisal approaches were used to determine whether the new spectrophotometric methods had an adverse environmental impact involving the Green Analytical Procedure Index (GAPI) and the AGREE (Analytical Greenness). These evaluations delivered information about the methods' eco-friendliness and sustainability, proving that they are in line with ecologically attributed practices. Furthermore, the Blue Applicability Grade Index (BAGI) was utilized to identify and verify the feasibility and practicality of the suggested approaches.

Nanoscale lipid-methylprednisolone conjugates: Effective anti-inflammatory, antioxidant, and analgesic agents

In this study, we have investigated new lipid-drug conjugates (LDCs) of methylprednisolone. Methylprednisolone is a corticosteroid, used for the potential treatment of inflammatory diseases. The LDCs 1–2; methylprednisolone palmitate (1) and methylprednisolone palmityl carbonate (2), were designed by conjugating a C16 aliphatic chain via an ester or carbonate bond, respectively. Their structures were comprehensively characterized using mass spectrometry, nuclear magnetic resonance spectroscopy, and infrared spectroscopy. These LDCs 1–2 were subsequently formulated into nanoscale particles (NPs) using ethanol injection method. Hydrogenated soybean phosphatidylcholine (HSPC) and tween-80 served as excipients in the NPs formulation. Characterization via dynamic light scattering, scanning electron microscopy, and atomic force microscopy confirmed the formation of spherical NPs with a diameter ranging from 100 to 120 nm. The LDCs NPs 1–2 exhibited excellent stability for about a month, with good polydispersity (around 0.2) and a negative zeta potential between −20 mV and −34 mV. Encapsulation efficiency of the LDCs within the LDCs NPs 1–2 surpassed 90 %, as determined by HPLC analysis. In vitro cytotoxicity studies utilizing LPS-activated THP-1 cells demonstrated no adverse effects associated with LDCs NPs 1–2 at concentrations up to 100 μg/mL. Furthermore, the LDCs NPs 1–2 effectively retained the anti-inflammatory activity, as evidenced by the suppression of IL-1β, TNF-α, and MCP-1 secretion in LPS-stimulated THP-1 cells. The therapeutic potential of these LDCs NPs 1–2 was further evaluated in rat intervertebral disc-derived nucleus pulposus cells (NPCs). Curative and preventive treatment regimens with the free drug and LDCs NPs 1–2 were employed. Quantitative PCR analysis revealed a significant downregulation of pain and inflammation markers (Substance P and COX-2) along with a concomitant upregulation of antioxidant markers (GPX1, PRDX1, and SOD1) in NPCs treated with both the drug and LDCs NPs 1–2 compared to oxidative stress-induced and control NPCs. Our novel LDCs NPs 1–2 exhibited promising therapeutic potential for treating inflammatory and pain related complications, (including intervertebral disc degeneration). This promise stems from their multifaceted properties, encompassing anti-inflammatory, antioxidant, and analgesic effects. Further research is warranted to fully explore LDCs NPs 1–2 as potential drug candidates in future pre-clinical and clinical trials.

Explainable Machine Learning Models to Predict Gibbs-Donnan Effect During Ultrafiltration and Diafiltration of High-Concentration Monoclonal Antibody Formulations.

Evaluating the Gibbs-Donnan and volume exclusion effects during protein ultrafiltration and diafiltration (UF/DF) is crucial in biopharmaceutical process development to precisely control the concentration of the drug substance in the final formulation. Understanding the interactions between formulation excipients and proteins under these conditions requires a domain-specific knowledge of molecular-level phenomena. This study developed gradient boosted tree models to predict the Gibbs-Donnan and volume exclusion effects for amino acids and therapeutic monoclonal antibodies using simple molecular descriptors. The models' predictions were interpreted by information gain and Shapley additive explanation (SHAP) values to understand the modes of action of the antibodies and excipients and to validate the models. The results translated feature effects in machine learning to real-world molecular interactions, which were cross-referenced with existing scientific literature for verification. The models were validated in pilot-scale manufacturing runs of two antibody products requiring high levels of concentration. By only requiring a molecule's biophysicochemical descriptors and process conditions, the proposed models provide an in silico alternative to conventional UF/DF experiments to accelerate process development and boost process understanding of the underlying molecular mechanisms through rational interpretation of the models.

Titanium Dioxide (TiO2): A Versatile Excipient in Pharmaceuticals

Titanium dioxide (TiO2) is a commonly used excipient in pharmaceutical formulations, offering several benefits to pharmaceutical products. As a highly insoluble and thermally stable oxide, TiO2 is utilized as an opacifying agent and suspending agent to improve the appearance, stability, and bioavailability of pharmaceutical products. Its high refractive index and high surface area make it an excellent adsorbent and filler material, while its non-toxic and odorless nature ensures its safe use in pharmaceutical applications. Here, the authors deliberate the properties and major applications of TiO2 as a versatile excipient in pharmaceuticals. The mesmerizing physic-chemical features of TiO2 depend on the size and shape of particles. At present, TiO2 has added countless considerations as an auspicious photocatalyst due to its extraordinary features such as excellent photocatalytic, electronic, and optical features, high stability, and economical and non-toxic nature. Moreover, the benefits of using TiO2 as an excipient are discussed, including its ability to improve product appearance, stability, and bioavailability. The review also reports the challenges associated with TiO2, including environmental concerns and biocompatibility issues. However, the benefits of TiO2 far outweigh its drawbacks, making it an extensively accepted excipient in pharmaceuticals. Inclusively, this article aims to provide a comprehensive overview of TiO2 as an excipient in pharmaceuticals, highlighting its unique properties, several applications, and benefits.

Efficiency Assessment and Verification of Lisinopril by Spectrophotometry

The goal is to provide a UV approach that is easy to use, affordable, accurate, and requires less time to estimate the amount of lisinopril in pharmaceutical formulations in bulk. Even though HPLC techniques are recognized in pharmacopoeias, non-chromatographic techniques such simple coupling processes or chemical modifications of lisinopril were similarly effective. The approach is predicated on UV spectroscopic methodology. Pharmaceutical formulations containing lisinopril, an ACE inhibitor that is frequently used to treat heart failure and hypertension, require precise and effective analytical techniques for estimating its amount. This work developed and validated a UV spectrophotometric approach for the quantitative analysis of lisinopril in pharmaceutical formulations as well as bulk form. The technique takes advantage of lisinopril’s natural absorbance properties, with maximal absorption being seen at 223nm. A high correlation coefficient (r = 0.9997) was found in linearity studies done throughout a concentration range of 10-50µg/ml, showing excellent linearity and suitable for quantitative analysis. The International Conference on Harmonization’s (ICH) guidelines were followed during the method’s validation. A detailed evaluation was conducted on a number of parameters, including specificity, robustness, ruggedness, accuracy, and precision (including repeatability and intermediate precision). The method’s accuracy and dependability were validated by validation study results, which fulfilled the exacting standards needed for pharmaceutical analysis. The suggested method’s accuracy was further supported by recovery trials, which showed that it could precisely quantify lisinopril even in the presence of formulation excipients and contaminants. The method’s specificity was demonstrated by interference studies, which also guaranteed that co-existing chemicals frequently found in pharmaceutical formulations would cause little influence.

Polysorbate stability: Effects of packaging materials, buffers, counterions, and pH

Polysorbates, widely used excipients in drug formulations, present a stability challenge due to complex degradation processes. This study investigates the hydrolysis of polysorbate (PS) under temperature stress (50 °C), focusing on the impact of primary packaging materials (glass vs. plastic vials), buffers (histidine and acetic acid), counterions (chloride vs. malate), and pH (4–7). Our findings reveal that leachables from plastic vials inhibit PS degradation in both histidine and acetic acid buffers. Kinetic parameters derived from sigmoidal fitting suggest distinct degradation mechanisms for each buffer. Furthermore, the malate counterion with histidine displays inhibitory effects on PS hydrolysis. Principal component analysis was employed to identify key factors. These results highlight the critical role of excipients and packaging in PS stability, providing valuable insights for biopharmaceutical formulation development and a deeper understanding of PS degradation complexities.

Marine Drugs for Topical Nanoformulation and Cosmeceutical Applications

Marine sources, such as phytoplankton and zooplankton from seas or oceans that correspond to various marine ecosystems, are the sources of marine pharmaceuticals. These medications have been utilized as active ingredients in cosmeceutical formulas to treat a range of skin conditions. Cosmeceuticals, or cosmetic products with an active pharmaceutical ingredient that imparts therapeutic efficacy or has benefits similar to those of medicine for skin health, are characterized as cosmetics plus medicines. Algae, fungi, sea cucumbers, seaweed, corals, prawns, and other marine organisms can all produce medicinal components that effectively treat wrinkles, blemishes, aging, hyperpigmentation, and oxidation. Because these medications and sources are natural, they have few or no negative effects on the skin. The skin is the site of action for the topical distribution of marine medicines and cosmeceuticals to treat this condition. This study investigates a viable nano-delivery method for marine medications in cosmetics, providing long-term and practical means of improving skin health and treating dermatological issues. The focus of this review is on marine medications, their chemical components, cosmeceutical usage, and the pathophysiology of various dermatological conditions. Additionally, raw ingredients used as excipients in cosmeceutical formulations can be sourced from marine species. Because of massive industrialization, unsustainability has become a major research topic. Marine chemicals, on the other hand, are highly eco-friendly and sustainable. A thorough analysis of the literature in this area focuses on the effects of different marine chemicals on the skin, as well as on the physicochemical parameters and post-formulation evaluations. As far as current research and prospects go, the cosmetics and cosmeceuticals sector is a better fit for marine pharmaceuticals when treating skin conditions.

Selecting appropriate excipients for paediatric dosage form − Paediatric excipients risk assessment (PERA) framework – Part 1

Excipients are often the major component of the formulation that critically affect the dosage form, manufacturing process, product performance, stability and safety. They exert different roles and functions in a dosage form. Selecting excipients with appropriate safety and tolerability is a major hurdle in paediatric formulation development. The suitability of a particular excipient will be dependent on the context of its use with regard to the paediatric age range, acute versus chronic use, and clinical risk–benefit of the disease, active and excipient. Scientists are encouraged to apply the principle of risk–benefit to assess the suitability of excipients to the specific paediatric population. Indicative list of parameters that should be taken into consideration and hierarchy of information sources when assessing the excipients risks is provided by regulatory agencies. However, the approach to be taken and details of how the risk evaluation should be undertaken are lacking. There is a need for a systematic approach to selection of excipients and assessment of the risk of excipient exposure. The Paediatric Excipients Risk Assessment (PERA) framework developed and proposed in this paper provides a structured, systematic decision-making framework via customizable tools and processes that can help to improve the transparency and communications on the selection and justification of use of excipients in a paediatric formulation.