Excipient Compatibility Research Articles

Leveraging High-Throughput Analytics and Automation to Rapidly Develop High-Concentration mAb Formulations: Integrated Excipient Compatibility and Viscosity Screening

Abstract Background Formulation screening is essential to experimentally balance stability and viscosity in high-concentration mAb formulations. We developed a high-throughput approach with automated sample preparation and analytical workflows to enable the integrated assessment of excipient compatibility and viscosity of mAb formulations. Methods Ninety-six formulations of a trastuzumab biosimilar were screened by combining 8 types of excipient modifiers with 4 types of buffers across a pH range of 4.5 to 7.5. Key stability risks, including high molecular weight (HMW) aggregation and fragmentation, were thoroughly assessed along with viscosity at high concentrations. Additionally, several biophysical parameters were evaluated for their ability to predict stability or viscosity outcomes. Multiple linear regression was applied to fit the data and identify key factors. Results The optimal pH range for the trastuzumab biosimilar was found to be 5.0 to 6.5, based on opposing pH dependencies for stability and viscosity. Buffer type had a minor effect on viscosity and fragmentation but played a significant role in influencing HMW aggregates, with Na-acetate and histidine-HCl being the best candidates. The impact of excipient modifiers on viscosity, HMW, and fragmentation depended on both pH and buffer type, showing strong interactions among factors. Arginine-HCl and lysine-HCl effectively lowered viscosity of the trastuzumab biosimilar at pH levels above 6.0, while glycine formulations were more effective at reducing viscosity below pH 6.0. Histidine-HCl, arginine-HCl, and lysine-HCl lowered the risk of HMW aggregation, whereas formulations containing Na-phosphate or NaCl showed higher HMW aggregation. Formulations with arginine-HCl, lysine-HCl, and NaCl demonstrated a rapid increase in fragmentation at pH levels below 5.0, while Na-aspartate formulations showed increased fragmentation at pH levels above 6.5. Conclusion Hence, it is important to optimize the levels of each chosen excipient in the formulation study to balance their benefits against potential incompatibilities. This study serves as a foundation for identifying high-concentration antibody formulations using a high-throughput approach, where minimal materials are required, and optimized formulation design spaces can be quickly identified.

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.

Understanding Excipient-Induced Crystallization of Spray-Dried Amorphous Solid Dispersion

This study investigates the compatibility of excipients with the model system SDI-X and their role in the induced crystallization of the amorphous compound-X in tablet formulations. We aimed to establish a straightforward and practical screening approach for evaluating excipient-induced crystallization of SDI in tablet matrices. Three methodologies—binary powder mixture, binary compact, and bilayer tablets—were employed to qualitatively and quantitatively evaluate the recrystallization of SDI-X with various excipients under accelerated storage conditions. The results demonstrated that binary compacts, providing direct physical contact between SDI-X and excipients, are superior in reflecting realistic drug-excipient contact within pharmaceutical tablets, enabling a more accurate assessment of excipient-induced crystallization for SDI-X. In contrast, the broadly used conventional binary blends can significantly underestimate this risk due to insufficient proximity. In addition, the bilayer tablets further confirmed that crystallization initiates at the contact surface between SDI-X and the excipients. The study highlighted that not only hygroscopicity but also the type of excipient and its physical contact with SDI-X significantly influence the recrystallization extent and rate of SDI-X. Interestingly, less hygroscopic diluents such as mannitol and lactose induced much higher levels of crystallization of SDIs, contrary to expectations based on moisture content alone. This suggests that the excipient type and contact surface are more critical in inducing recrystallization than just the level of moisture. The findings emphasize the need for careful excipient selection, study design, and sample preparation to enable appropriate assessments of SDI-excipient compatibility.

Formulation and in-vitro anticancer activity of nilotinib immediate release and ibrutinib sustained release pellets

Background: Blood cancer is a significant contributor to mortality rates worldwide, and its prevalence is projected to rise on a global scale. This trend places considerable strain on healthcare systems and necessitates the expedited development of innovative treatments by pharmaceutical firms to remain competitive. Conventional pellets produce rapid plasma drug levels, but they might cause side effects, decrease effectiveness, and lead to poor therapeutic management. Ibrutinib and Nilotinib are employed to treat leukemia patients. Methodology: The current research aims to formulate, characterize, and anticancer effect of Nilotinib immediate release (NIR) and Ibrutinib sustained release (ISR) seal sugar-coated pellets. Micrometric properties estimated the characterization of the drug pellets, and surface morphology was estimated using scanning electron microscopy. Drug excipient compatibility studies, stability studies, and in-vitro drug release were accessed. Result & Discussion: The results of pellet formulations FNI-1 to FNI-5 showed that FNI-5 formulations showed 100±6.0 µm size and possessed excellent mechanical strength for giving pellets a good self-life; also, due to the higher drug content up to 99%, FNI-5 was the best suited for pellet formulation and because NIR showed 99.18 ± 2.12 drug release at 2h and ISR 99.03±3.74% up to 12h so that anticancer concentration maintained for prolonged period. The standard dose for cytotoxicity against the THP-1 cell line of Nilotinib was found to be 200 mg, and the maintenance oral dose of Ibrutinib was 140mg, with four times the intake of the drug up to 560 mg. In an in vitro study in FNI-5 (final formulation), the dose of Ibrutinib was reduced to 420 mg. Conclusion: A synergistic effect of Ibrutinib and nilotinib drugs was observed in the inhibition of cancer cell growth, with an IC50 value of 4.585 µg/mL

Formulation and Evaluation of Bilayered Floating Tablets of Aceclofenac

The objective of this study was to create and assess homogeneous bilayered floating tablets of aceclofenac in order to increase the drug's bioavailability and prolong its stomach release. One of the nonsteroidal anti-inflammatory drugs (NSAID) common side effects is poor solubility and minimal stomach retention, which makes it difficult to treat effectively. As matrix-forming polymers, ten formulations (F1–F10) were made with different amounts of HPMC K15 and additional excipients. Physical properties, buoyancy, in vitro drug release, and kinetic modelling were evaluated for each formulation. With a floating lag time of less than one minute and buoyancy maintained for more than 12 hours, Formulation 5 (F5) showed the most promising findings. With 97.01% of aceclofenac released over 12 hours, it showed a regulated drug release pattern that followed the Korsmeyer-Peppas release model well (R2 = 0.9242). Pre-compression and post-compression values for the optimised formulation F5 were adequate, suggesting good flow characteristics and tablet integrity. FTIR spectroscopy was used to verify the drug-excipient compatibility, guaranteeing stability and the lack of interactions. According to these results, aceclofenac's homogenous bilayered floating tablets, specifically formulation F5, may be able to improve gastric retention time and offer a sustained release profile. This could mean that the medication can be used to treat chronic inflammatory conditions more effectively and with better patient compliance. Keywords: gastric retention, bioavailability, drug excipient compatibility.

Developing Self-Nanoemulsifying Drug Delivery Systems Comprising an Artemether-Lumefantrine Fixed-Dose Combination to Treat Malaria.

Despite attempts to control malaria, poor drug bioavailability means malaria still places enormous pressure on health globally. It has been found that the solubility of highly lipophilic compounds can be enhanced through lipid formulations, e.g., self-emulsifying drug delivery systems (SEDDSs). Thus, quality-by-design and characterization were used to justify the development and determine the feasibility of oral oil-in-water SEDDSs comprising a fixed-dose combination (FDC) of artemether-lumefantrine to treat malaria more effectively without the aid of a fatty meal. These formulations were compared to a commercial product containing the same active compounds. Excipient compatibility and spontaneous emulsification capacity of different FDC-excipient combinations were identified by employing isothermal microcalorimetry, solubility, and water titration tests. Pseudoternary phase diagrams were constructed, and checkpoint formulations were selected within the self-emulsification region by reviewing formulation properties essential for optimized drug delivery. SEDDSs capable of enduring phase separation within 24 h were subjected to characterization experiments, i.e., drug concentration determination, cloud point, droplet size, size distribution, self-emulsification time, self-emulsification efficacy, viscosity, zeta potential, and thermodynamic stability analysis. SEDDSs with favorable characteristics were identified in the micro or nano range (SNEDDSs) before being subjected to drug release studies. All final formulations depicted enhanced artemether and lumefantrine release compared to the commercial product, which could not release lumefantrine at a quantifiable concentration in this study. The avocado oil (AVO)4:6 and olive oil (OLV)3:7 SNEDDSs overall portrayed the ideal characteristics and depicted the highest percentage of drug release. This study offers evidence that SNEDDSs from selected natural oils comprising an artemether-lumefantrine FDC can potentially enhance the bioavailability of these lipophilic drugs.

Mixture Experimentation in Pharmaceutical Formulations: A Tutorial.

Mixture experimentation is commonly seen in pharmaceutical formulation studies, where the relative proportions of the individual components are modeled for effects on product attributes. The requirement that the sum of the component proportions equals 1 has given rise to the class of designs, known as mixture designs. The first mixture designs were published by Quenouille in 1953 but it took nearly 40 years for the earliest mixture design applications to be published in the pharmaceutical sciences literature by Kettaneh-Wold in 1991 and Waaler in 1992. Since then, the advent of efficient computer algorithms to generate designs has made this class of designs easily accessible to pharmaceutical statisticians, although the use of these designs appears to be an underutilized experimental strategy even today. One goal of this tutorial is to draw the attention of experimental statisticians to this class of designs and their advantages in pursuing formulation studies such as excipient compatibility studies. We present sufficient materials to introduce the novice practitioner to this class of design, associated models, and analysis strategies. An example of a mixture-process variable design is given as a case study.

Assessing the Compatibility of Menatetrenone with Excipients: A Spectroscopic Approach and Implication in Drug Formulation Development.

An experiment was conducted to evaluate the compatibility of menatetrenone with selected pharmaceutical excipients. Fourier Transform Infrared Spectroscopy (FTIR) was used to assess drug-excipient compatibility. The present research systematically investigates the FTIR spectrum of each chemical compound separately and their physical blends, analyzing for possible shifts, alterations or novel peak that may indicate chemical interactions. This study aims to utilize spectral data interpretation to detect potential compatibility problems that may occur while design and production of menatetrenone containing dosage forms ensuring their increased stability and effectiveness. The FTIR results demonstrated that all the pharmaceutical excipients were compatible with menatetrenone. In conclusion, the compatibility of pharmaceutical excipients with menatetrenone was successfully assessed using FTIR that will aid in future design of formulations containing menatetrenone as therapeutic moiety.

Reactivity of N terminal histidine of peptides towards excipients/impurity of excipients: A case study of liraglutide excipient compatibility study

The selection of quality excipients is a crucial step in peptide formulation development. Apart from excipient incompatibility, process-related impurities or degradants of an excipient can interact with peptide-active pharmaceutical ingredients, forming the interaction products. The formaldehyde has been reported as an impurity of excipient in polyethylene glycol, glycerol, magnesium stearate, microcrystalline cellulose, mannitol, etc. The peptide contains various amino acids such as histidine, lysine, and arginine having free amine groups. These amine groups act as strong nucleophile and can increase the reactivity of peptides. PLGA is the most widely used biodegradable polymer in sustained-release formulations. The hydrolysis of PLGA generates glycolic acid and lactic acid impurities, which can form the interaction product with the amines of peptides. During the formulation development of Liraglutide, we have found few interaction products. The systematic characterization and mechanistic understanding of these interaction products lead us to imidazopyrimidine, glycolyl, and lactolyl moieties. These interaction products have been characterized thoroughly with the use of LC-HRMS, MS/MS, and hydrogen-deuterium exchange mass studies. The study revealed that the reactivity of N-terminal histidine must be considered for formulation development. Moreover, the quality of excipients with respect to presence of impurities must be considered as critical material attributes.

ZINC PECTINATE-SESBANIA GUM-MEDIATED INTERPENETRATING POLYMER NETWORK-BASED MICROBEADS AS A CANDIDATE FOR FLOATING DRUG DELIVERY OF ESOMEPRAZOLE

This study aimed to develop esomeprazole-loaded zinc-pectinate-Sesbania gum floating microbeads, optionally supplemented with calcium silicate, as a gastro-retentive drug delivery system. The microbeads were produced using the ionic gelation method, with zinc acetate as the crosslinking agent, and were characterized through in vitro studies. The findings revealed that all formulations exhibited high drug encapsulation efficiency and sustained drug release profiles. Polymer ratios, calcium silicate incorporation, and the choice of low-density oils significantly influenced drug encapsulation efficiency and release kinetics. Notably, the B:6 batch, formulated with Sesbania gum and low methoxy pectin, demonstrated outstanding performance, releasing 95.89 ± 1.66% of the drug within 7 h, with a floating lag time of 1.18 ± 0.07 min, indicating promising in vitro gastro-retention capabilities. Analysis of P-XRD, FT-IR, SEM, and DSC data highlighted changes in crystallinity, drug–excipient compatibility, surface morphology, and thermal behavior of esomeprazole and esomeprazole-loaded microbeads. In conclusion, these floating microbeads represent a potential gastro-retentive drug delivery system, offering enhanced buoyancy and prolonged drug release, with potential therapeutic advantages for peptic ulcer management.

Impact of Penetration Enhancer and Natural Oil on Transdermal Delivery of Modified Karaya Gum Gel

The etodolac based modified karaya gum (MKG) gel was developed using 32 factorial design to enhance the therapeutic effect of gel to treat inflammation. Gels were prepared with different concentrations of MKG and arachis oil using 32 factorial design. The percentage of drug content was found in the range of 96 to 99%, viscosity results shown in the range of 842 CPS to 2560 CPS and in vitro drug release was found to be in range of 38% to 98% respectively. Whereas ex-vivo permeation studies of etodolac gel and pure etodolac solution across the burned pig skin were shown 72% and 42% respectively. The drug and excipient compatibility studies by FTIR confirms that, there is no major functional group change was observed. The results concluded that, the combination of MKG and arachis oil were improved the penetration of etodolac through burned pig skin thereby the combination of PE and oil successfully enhanced the therapeutic effect of etodolac.

Incorporation of standardised extract of Curcuma longa Linn into phytosomes and its evaluation for in vitro Anti-inflammatory potential and Brine shrimp lethality assay

Aim: To incorporate standardized Curcuma longa Linn extract into phytosomes and evaluate for in vitro anti-inflammatory and BSL bioassay. Method: The quality of the plant material was determined by various pharmacognostic parameters. The plant material was then subjected to maceration for extraction using ethanol: water as solvent followed by Soxhlet extraction. The resulting extract was subjected to phytochemical analysis to determine the presence of plant metabolites. The drug and excipients compatibility was evaluated by FTIR study. Furthermore, using the thin film hydration approach, a new lipid-based phytosome was prepared. In vitro anti-inflammatory and brine shrimp lethality tests were performed on prepared phytosome. Results: Moisture content, total ash, acid insoluble ash, water soluble ash values, aqueous, alcohol, and petroleum ether extractive values are all found to be within limits. The phytochemical analysis validated the existence of alkaloids, tannins, resins, carbohydrates, proteins, flavonoids, and saponins. The compatibility study demonstrates the compatibility of excipients with drugs. Thin film hydration technique was employed successfully to prepare the phytosomes containing Curcuma longa linn extract. In vitro anti-inflammatory activity revealed that prepared phytosome could serve as natural based therapeutic option for anti-inflammatory potential. Brine shrimp lethality assay also confirmed the bioactivity of prepared phytosomes. Conclusion: The method used for standardization can be used to aid with plant identification and quality analysis of Curcuma longa Linn for future research. It can be inferred from the findings that phytosomes loaded with Curcuma longa Linn extract exhibited promising anti-inflammatory and cytotoxic effects.

Formulation Development and Evaluation of Ubidecarenone Chewable Tablet

Background: Coenzyme Q10 has a role in mitochondrial transport system and can be utilized as a supplement in migraine prevention. This study's objective is to assess Coenzyme Q10's effectiveness when used in conjunction with conventional medications to prevent migraines. Adding 300mg of coenzyme Q10 each day to prescription medications, while another group of patients continued receiving standard care. Over the course of a three-month treatment period, data on attack frequency, headache pain intensity, monthly migraine days, and associated symptoms like nausea, vomiting, phonophobia, and photophobia were analyses. Ubidecarenone, a medicinal component. The goal is to produce Ubidecarenone in a 300 mg chew-able tablet form. In vitro release studies and organoleptic properties, such as taste and flavour, will be evaluated. investigations in the early stages, tests for medicine excipient compatibility, and analyses of the water content Quality Assurance for the Process Hausner's Ratio, Bulk Density, Tapped Density, Comprehensibility Index, and Angle of Repose for calculating derived properties for medications and mixtures. ingredients that have been optimised for their concentrations, such as tastes, sweeteners, disintegrants, wetting agents, glidants, and lubricants. putting the best possible ingredients together to make a chew able pill. Evaluation of chewable tablets for post compression parameters including uniformity of weight, thickness, hardness, brittleness, friability, dissolution, assay, and in vitro drug release properties. An evaluation of the optimised batch's palatability is required. The intention is to create chewable tablets of ubidecarenone. Method: The wet granulation method is used to make chewable tablets of ubidecarenone. Mannitol is used as a diluent, crospovidone as a disintegrant agent, sodium starch as a disintegrate agent, saccharin sodium as a sucrose sweetener, orange flavour, peppermint oil as a flouring agent, and colloidal silicon dioxide as a gliding. The Ubidecarenone (300 mg) is one of the best first-line treatments for migraine prevention.

Formulation and Evaluation of Pulsatile drug delivery of Albuterol sulphate and Theophylline drugs using modified Pulsincap technology

Albuterol Sulphate and Theophylline are used as anti-asthma agents. The objective of the present investigation was to design develop and evaluate a modified pulsincap drug delivery system of Albuterol Sulphate and Theophylline for the treatment of Asthma. The body of capsule was made insoluble with water by cross linking with formaldehyde. This modified capsule was completely filled with drug with polymer such as HPMCK15M, HPMC K 100M, PVPK-30 to expel the drug after predetermined lag time. A hydrogel plug was inserted in the body of a capsule to obtain desired drug release after a lag time for chronotherapy of asthma. Untreated capsule was attached to the treated body and was released. The drug was exerted to precompression parameter such as Angle of repose, Bulk density, Tapped density, Car’s index Hassner’s ratio. These capsules were subjected to further post formulation studies such as weight variation, drug content, invitro dissolution studies separately. The pre and post formulation parameters were found to be within permissible limit. The mere compatibility of drug, polymer and excipients were determined by Fourier transform infrared analysis (FTIR) and UV-Visible spectroscopy (UV). The results showed that drug was completely compatible with polymer and excipients. In vitro dissolution were carried out by using pH 6 .8 and pH 7.4 buffers. Based on the result obtained F5 Formulation shows good dissolution profile. Higuchi, Hixson crowell. Koresmeyer peppas to evaluate the kinetics and drug release. The drug release follows first order kinetics and the mechanism was found to be NON FICKS DIFFUSION.
 Keywords: Albuterol Sulphate, Theophylline, modified pulsincap drug delivery system, FTIR, Dissolution

Varenicline and Maltodextrin Combination: A Promising Approach for Reducing Nitrosamine Impurities in Solid Dosage Forms

This research article investigates the use of varenicline and maltodextrin combination to reduce the nitrosamine impurities in varenicline tablets, a medication used to treat nicotine addiction. Nitrosamines are carcinogenic compounds that have been found in varenicline, raising concerns about its safety. Drug excipient compatibility was initially performed with all possible excipients, including maltodextrin, to identify potential approaches for reducing nitrosamine impurities. The results showed that maltodextrin was more effective than other excipients in reducing nitrosamines in the drug product. This finding provided an indication for the use of maltodextrin as a potential solution to the nitrosamine problem in varenicline tablets. The study involved preparing varenicline-maltodextrin formulations and analyzing the formulations for nitrosamine impurities. The finished formulation was prepared by simple mixing of varenicline, maltodextrin, disintegrant, filler, lubricant, and compression using suitable tooling, followed by aqueous film coating. The formulated tablets were tested for assay, content uniformity, dissolution in release media, and multimedia, and the results were found to be satisfactory. The results showed that the varenicline-maltodextrin combination significantly reduced nitrosamine content, and all other parameters were satisfactory. In addition, the nitrosamine impurity levels were significantly reduced to less than 3 ppm after 30 days of storage at 50±2°C/75±5 % RH. Moreover, more than 85% of drug release was observed in all tested release media, meeting the predefined specifications for BCS-based biowaiver. These findings suggest that the use of varenicline and maltodextrin combination is a promising approach to improve the safety of varenicline.

Reverse‐phase high‐performance liquid chromatography methodology for film‐forming mafenide spray: Compatibility, assay, and in‐vitro release evaluation using Franz vertical diffusion cell apparatus

AbstractThis paper described a short and precise reverse‐phase high‐performance liquid chromatography (HPLC) method for quantifying mafenide in a film‐forming spray and preliminary in‐vitro release study. Following the International Council for Harmonization guidelines Q2 (R1), the method was validated. The chromatographic separation was achieved using a 10 mM potassium dihydrogen phosphate solution (mobile phase A) mixed with HPLC‐grade methanol (mobile phase B) in an 85:15 v/v ratio. Inert Sustain C8 (4.6 × 250 mm), 5 μm column was selected as the stationary phase. The flow rate was set as 0.8 mL/min, and detection was carried out at a wavelength of 222 nm. The developed HPLC method showed an accuracy between 98% and 102%. The primary diffusion study of film‐forming spray was performed using the Franz vertical diffusion cell apparatus. It was observed that an average of 26.94% of drug releases at 24 h. This indicates the drug has a slower release rate and shows local pharmacological action. The Weibull dissolution model was more fitting with regression square 0.9953. Furthermore, the drug excipient compatibility study revealed no interactions as the only drug peak was found in the chromatographic method, indicating that the chosen excipients were appropriate for a stable formulation.

Development of Pharmaceutical Equivalent Montelukast Sodium Immediate-Release, Film-Coated Tablets

Montelukast tablets are sold under the brand name Singulair and are used to control and prevent asthma symptoms. In this study, 10 mg film-coated montelukast tablets were developed as a generic drug in order to evaluate the pharmaceutical equivalent of the innovator’s products. The primary formulation ingredients used in all developed formulations (F1-F5) were the same as those described in the Singulair tablet package insert, except for formulations F3, F4, and F5, to which solubilizing enhancers were added to increase montelukast solubility. The core tablets were produced using the wet granulation method before being coated with HPMC polymer. FT-IR and DSC were used to determine drug and excipient compatibility. The micromeritic properties of the granules were assessed. The physicochemical properties of generated montelukast tablets and Singulair tablets were also investigated. The dissolution profiles of the tested drug and the innovator were assessed in a variety of pH mediums (pH 1.2, 4.5, 6.8, and water). The similarity (f2) and difference (f1) factors were computed. The accelerated and long-term stability of the tested drug in hot and humid climate zones was evaluated. The analytical method validation used in this study was ICH-acceptable for 8 parameters including specificity, range, linearity, accuracy, precision, limit of detection, limit of quantitation, and robustness. F1-F5 granules had similar properties, such as a pale-yellow color and excellent flow properties. There were no chemical interactions between montelukast and the excipients according to FT-IR and DSC analyses. The physical properties of all developed montelukast film-coated tablets were similar (average weight 212-218 mg; thickness 3.02-3.07 mm; assay 101-102% LA; disintegration time 3-4 min), except that the disintegration time of F3 was 8.10 min and that of F5 was 5.90 min, which was caused by the addition of poloxamer 188 to the formulation. In all mediums, only the F1 formula produced acceptable comparison dissolution profiles to Singulair. After 6 months of storage under accelerated and long-term conditions, the results showed the F1 formulation remained physically and chemically stable.

Current Challenges and Approaches on Delivery of Protein Based Formulations

Numerous obstacle crops up in the path of developing efficient protein-based formulations and administration in humans for their therapeutic effect. The challenges starts from protein synthesis to it’s handling procedure, stability, storage, excipients compatibility, scale up, analysis, validation, tissue targeting, in-vivo bioavailability, immunogenic reactions, etc., In the field of protein drug development, various novel methods and techniques have been evolved and continuing the research to face those challenges to bring out potential drug formulations and its delivery system to the market. It is vital to develop various strategies for protecting the integrity of proteins, increasing their availability in the body, decreasing immunological responses, transporting and target to particular tissues or cells. This current review focuses on to understand the problems, challenges encountering and the best approaches for protein based drug formulation development. It is one of roadmap to plan various research activities for continual improvement of therapeutic applications of newly developing protein drugs in this area.

A Rapid 3-Day Excipient Screening Methodology and its Application in Identifying Chemical Stabilizers for Solid Formulations with Mixed Mechanisms of Degradation.

This study outlines a practical approach for assessing chemical instability by heating the drug-excipient binary mixtures or multi-excipient formulations at 75°C for 3days before characterization. Differentiating itself from other excipient compatibility methods, our methodology necessitates a saturated aqueous slurry rather than arbitrarily fixed water content. This allows bulk and surface water in the excipient to contribute to drug degradation. The synergistic impact of surface water and elevated temperature expedites degradation kinetics, resulting in accelerated data generation. Among excipient compatibility methods available, our method is quantitative and merges with traditionally used methodologies. The devised nomograph enables extrapolation of shelf life at 20°C from experimental data obtained at 75°C. This methodology also helped identify stabilizers for the drug NVS-1 where traditional excipient compatibility programs had failed. Incorporation of monovalent salts, such as sodium/potassium chloride and sodium bicarbonate at 5% w/w, significantly enhanced the chemical stability of NVS-1, ensuring stable tablet formulations. Our hypothesis posits that stabilization is due to increased ionic strength in the slurry, which stabilizes an induced dipole within the polar NVS-1 drug. Additionally, the presence of ions in the moisture layer is anticipated to stabilize π-π stacking of two planar aromatic NVS-1 molecules. The expedited generation of experimental data allowed the identification of inorganic salts to supplement a standard excipient compatibility screening panel. Considering the economic implications of stability testing methodologies in effort, cost, and duration, a faster turnaround in chemical stability data enhances formulation selection. This ultimately facilitates the development of drug formulations with greater efficiency without delays.

Design and characterization of nano sponges loaded vaginal gels of Voriconazole

Objectives: The current inquiry of this research job is to build and analyze a bio adhesive vaginal gel that is packed with Voriconazole Nano sponge for an extended residence duration at the point of infection, resulting in a positive drug release profile. Methods: Nano sponges were created using a solvent evaporation process in varied Voriconazole to β-cyclodextrin ratios. Zeta possibility, polydispersity, size of particles analysis, capture efficiency, and surface morphology of Nao sponges are all determined using scanning microscopes with electrons (SEM). FTIR and DSC investigations were used to determine drug excipient compatibility. Carbopol/Hypromellose/Sodium Carboxymethyl cellulose/HPC has been used to make the bio adhesive gel, while both propyl paraben and a methyl para were employed as antioxidants. Triethanolamine, also was used to regulate the pH, resulting in a transparent gel. The gel base has been incorporated with the improved Voriconazole Nano sponge mixture. The pH, viscosity, spread ability, extrudability, and medication content of Nano sponge in mixes of gels were all investigated. The gel's in vivo diffusion has been examined on goat vaginal mucosal. Cellophane membranes was used in an artificial drug release examination. Results: The improved generation of IDLNS12 Nano sponge (drug-polymer ratio 1:1) demonstrated 91.56% entrapment efficiency. The average particle diameter of all formulations was less than 310 nm. The SEM photographs revealed smooth and spherical particles. INSG4 (Carpool and HPC) gel formulation had a viscosity value of 4529 cps at 2-10 RPM, a gel strength of 92.65N load, and an expansion speed of 37.24 g.cm/seconds. At 12.0 minutes, INSG4 achieved 99.98% drug release. And a mucous adhesive time of in excess of 12 hours. Conclusion: These results suggest that Voriconazole-loaded β-cyclodextrin Nano sponge in mucous adhesive gel might be used for managing infections of vagina perpetually.