Poloxamer 188 (P188) as a non-ionic surfactant is used in proteinaceous formulations to prevent protein adsorption to hydrophobic surfaces and unfolding at interfaces, preventing the formation of aggregates and particles. Its chemical intactness is crucial to the stability of drug products due to its protecting effects at interfaces. In order to identify and mitigate potential risks that might cause the degradation of P188 during the manufacturing process and storage, in the current work, the stability of P188 was investigated by forced degradation in buffered formulation conditions via oxidation and thermal stress conditions. The process of degradation was monitored through the dedicated liquid adsorption chromatography (LAC) with high sensitivity, and the degradants were characterized by high-resolution mass spectrometry. Results suggest that the vulnerability of P188 is largely related to the buffer conditions. Histidine promotes degradation in the presence of hydroxyl radicals but inhibits the degradation in the presence of H2O2 and alkyl radicals. In thermal stress conditions, histidine protects P188 from degradation at 40 °C, and activates its decay only at higher temperature, like 60 °C.

We previously developed a triazole modified tetraiodothyroacetic acid (TAT) conjugated to a polyethylene glycol (PEG)-based thyrointegrin αvβ3 antagonist targeted compound, called P-bi-TAT. It exhibited potent anti-angiogenic and anticancer activities in vivo. The objective of the current study is to develop a quantitative bioanalytical method for P-bi-TAT using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and to elucidate pharmacokinetics (PK) and biodistribution of P-bi-TAT in animals. We used in-source collision-induced dissociation (CID) for ionization of P-bi-TAT in the positive mode, followed by multiple reaction monitoring (MRM) for quantification. P-bi-TAT was quantified using P-mono-TAT as an internal standard because of its similarity in structure and physicochemical properties to P-bi-TAT. The LOQ for P-bi-TAT was 30 ng/μL and the recovery efficiency was 76% with the developed method. Cmax and AUC results at different doses (1, 3, 10 mg/kg) in rats suggest that P-bi-TAT is dose-dependent within the range administered. Results for Cmax and AUC in monkeys at a low dose (25 mg/kg) were comparable to those in rats. Biodistribution of subcutaneously administered P-bi-TAT in the brain of rats ranged from 7.90 to 88.7 ng/g brain weight, and levels of P-bi-TAT in the brain were dose-dependent. The results suggest that P-bi-TAT is a potential candidate as a molecular-targeted anticancer therapeutic with blood-brain barrier permeability and acceptable PK parameters. Its accumulation in organs, toxicokinetic, and pharmacodynamics needs to be further investigated.

The advent of recombinant protein-based therapeutic agents in the 1980s and subsequent waves of innovation in molecular biology and engineering of biologics has permitted the production of an increasingly broad array of complex, high molecular weight constructs. While this has opened a powerful new toolbox of molecular scaffolds with which to probe and interdict biological processes, it also makes deciphering the architectural nuances between individual constructs intuitively difficult. Key to downstream data processes for the detection of data trends is the ability to unambiguously identify, compare, and communicate the nature of molecular compositions. Existing small molecule orientated software tools are not intended for structures such as peptides, proteins, antibodies, and RNA, and do not contain adequate atomistic or domain-level detail to appropriately convey their higher structural complexity. Similarly, there is a paucity of large molecule-focused data analysis and visualization tools. This article will describe four new approaches we developed for the graphical representation and analysis of complex large molecules and experimental data. These tools help fulfill key needs in scientific communication and structure-property analysis of complex biologics and modified oligonucleotide-based drug candidates.

Fingolimod is an oral agent approved for the treatment of relapsing forms of multiple sclerosis (MS), which has demonstrated efficacy in Phase III trials in patients with relapsing-remitting MS (RRMS). The present study was designed to assess bioequivalence between a fingolimod Test capsule formulation (Teva Argentina, formerly IVAX Argentina S.A.) and a Reference capsule formulation (Novartis Pharma GmbH, Germany). In a single-center, randomized, single-dose, open-label, two-way crossover study under fed conditions, 16 healthy volunteers were randomized to receive a single oral dose of 0.5 mg of the Test and Reference formulations, with a 42-day washout period between administrations. The three pharmacokinetic (PK) parameters employed in the study to assess the bioequivalence between the Test and Reference formulations were maximum plasma concentration (Cmax), time to Cmax (Tmax), and area under the concentration–time curve from time zero to 72 h (AUC0–72). No significant differences between the Test and Reference formulations for any of the three PK parameters were observed. Based on 90% geometric confidence intervals (CIs) within 80% to 125% for both AUC0–72 and Cmax, the Test and Reference formulations were considered bioequivalent.

An American Association of Pharmaceutical Scientists (AAPS) workshop on stability challenges for clinical supplies and commercial distribution of drug product that are not addressed in the International Conference on Harmonization (ICH) Quality documents was held from April 3rd – 4th, 2017 in Rockville, MD. Seventeen subject matter experts (SME), from industry and the Food & Drug Administration (FDA) presented and facilitated the round-table discussions. A total of fifty-five participants that included experienced pharmaceutical scientists, both from small and large pharmaceutical companies and service providers, benefited from the opportunity to interact face-to-face with industry partners and regulatory agency SMEs. The two-day meeting was divided into five major sections to ensure face-to-face interactions and round-table discussions between participants and SMEs: 1) statistical approaches to stability, dissolution, and shelf life testing, 2) microbiological quality of drug products, 3) strategies to support distribution, unplanned excursions, and transportation of drug products, 4) regulatory considerations on stability testing of biologics, and 5) in-use stability during clinical and commercial phases. All in all, this interactive workshop focused on challenges and successes of addressing stability concerns that affect pharmaceutical development, manufacturing, distribution, and use of drug substances/products for which no or limited ICH guidance exists. The interactive meeting provided a unique opportunity to industrial scientists and regulatory agency liaisons to facilitate the discourse on how to address stability challenges that are not addressed in harmonized guidelines: this paper summarizes those discussions.

Anti-drug antibodies (ADAs) can interfere with ligand binding assays (LBAs) by binding to epitopes recognized by the assay antibodies or by preventing assay antibody binding through steric hindrance. This can lead to underestimation of total drug concentration in pharmacokinetic (PK) samples which can confound decisions during drug development. We hypothesized that ADA interference in LBAs can be removed by sample heat pre-treatment. We heat pre-treated ADA-spiked samples by incubating them in a shallow water bath at 56–100 °C for 5–30 min prior to measuring the samples by a traditional electrochemiluminescence (ECL) assay. Heat pre-treatment at minimum 85 °C for 5 min completely removed the ADA interference. We then compared the analyte concentrations measured with and without heat pre-treatment of blood samples from toxicology studies performed for two different analytes in 60 cynomolgus monkeys and 29 minipigs, respectively. The overall difference in measured concentration of ADA-positive samples was significantly different from the overall difference in measured concentration of ADA-negative samples. For the cynomolgus monkey study samples, the ADA titer was determined, and the difference in measured concentration, when comparing heat pre-treatment to no heat pre-treatment, was significantly correlated to the ADA titer. Additionally, heat pre-treatment removed parallelism issues observed in a subset of study samples. Our data suggest that sample heat pre-treatment can abolish ADA interference in an LBA and could serve as a tool to assess the degree of ADA interference and the total drug concentration in a PK sample. Of note, before utilizing this strategy on a new analyte, it is necessary to assess whether heat pre-treatment negatively affects the detection of the analyte by the assay antibodies.

Dostarlimab is a humanized anti–PD-1 monoclonal antibody. Dostarlimab (JEMPERLI; TSR-042) was recently approved in the USA and in the EU. The presence of neutralizing antibodies (NAbs) is a cause for concern because they block the therapeutic function of the antibody and reduce drug efficacy. Therefore, programs developing therapeutic biologics need to develop and validate assays that adequately assess the presence of NAbs in the serum of patients treated with biologic therapies. Presented here is the development and validation of a competitive ligand-binding assay that specifically detects anti-dostarlimab NAbs in human serum. Precision, sensitivity, hook effect, selectivity, assay robustness, stabilities, and system suitability were evaluated. In addition, drug tolerance of the assay with the implementation of a drug removal process was investigated. The cut point factor for the detection of NAbs in human serum at a 1% false-positive rate was determined. The assay’s precision, sensitivity, hook effect, selectivity, robustness, and drug interference were tested and found to be acceptable. With system suitability and stability established, this assay has been used to evaluate NAbs to guide the development of dostarlimab. Trial registration: Clinicaltrials.gov, NCT02715284 . Registered 9 March 2016

Human absorption, distribution, metabolism, and excretion (hADME) studies of new drugs are required for global regulatory filings. Recent advances in high sensitivity analytical technologies have enabled microtracer hADME studies wherein very low radioactive doses can be administered to healthy volunteers to study drug pharmacokinetic profile. Microtracer hADME studies are advantageous to accelerate study timelines during drug development. However, there are limited examples in peer-reviewed journals that highlight the key chemistry, manufacturing, and control (CMC) development challenges and requirements for enabling these clinical microtracer hADME studies. The current manuscript summarizes the CMC activities, risk assessment, and mitigation strategies that were put in place and executed to enable and accelerate the microtracer hADME study of [14C]-labeled sotorasib (AMG 510, compound 1). Sotorasib is a first in class KRASG12C inhibitor used to treat non-small cell lung cancer (NSCLC) in patients with a KRASG12Cmutation (Canon et al., Nature 575:217–223, 2019). The key CMC activities included the synthesis of low nanocurie [14C]-labeled AMG 510 drug substance, development of a drug-in-bottle (DIB) formulation, use of simulation software to predict absorption profiles, associated drug substance and drug product analytical control strategies development, and the utilization of accelerator mass spectrometry (AMS) as a CMC tool enabling low radioactive strength formulation analysis.

The aim of this study was to investigate powder mechanics upon compression using data obtained from force-displacement (F-D) curves. The Kawakita model of powder compression analysis was adopted in order to compare the pressure-volume reduction relationship of the drug powders in relation to the F-D curves. Experiments were carried out on six model drugs (metronidazole, metformin, secnidazole, ciprofloxacin, norfloxacin, and mebeverine). The drugs were compressed at different pressures in the non-processed or processed (using a roller compactor) forms. Results indicate the similarity between the F-D curves and a rearranged form of the Kawakita model. The foregoing enables the calculation of two important powder parameters, “a” (maximum powder volume reduction) and “Pk” (pressure required to achieve half of the maximum volume reduction) from the F-D curves without the need, as in the case of the conventional Kawakita model, to compress powders into tablets at different compression forces.

Ion chromatography (IC) has evolved into one of the most widely used separation techniques of analytical chemistry. Consequently, the number of users of this method is continuously growing. Analysts often assume that widely used guidelines for HPLC method validation in regulated environments routinely apply to IC. This manuscript provides an analysis of the potential shortcomings of traditional approaches to development and validation of IC methods using suppressed conductivity detection and a risk-based alternative approach to these activities. The goal of the alternative approach is a reduction in the risk of erroneous determinations of analytes when IC methods using suppressed conductivity detection are employed.

The COVID-19 pandemic has led to increased usage of hand sanitizer products by the public to prevent the spread of COVID-19 and decrease the likelihood of acquiring the disease. The increase in demand has also led to an increase in the number of manufacturers. This work describes the FDA’s Center for Drug Evaluation and Research (CDER) laboratories efforts to develop tests to assess the quality of hand sanitizer products containing ethanol or isopropanol as the primary active ingredient. The products were evaluated for the active ingredient content and determination of the 12 impurities listed in the FDA Hand Sanitizer Temporary Guidance, followed by a spike recovery assay performed to verify the test results. Extensive method development was conducted including an investigation into the stability of ethanol, isopropanol, and the 12 impurities. Stability and kinetic studies confirmed the instability of acetal in acidic liquid hand sanitizer products during spike recovery assay testing. The headspace GC-MS method was validated according to ICH Q2 (R1) guidelines and the spike recovery assay was validated using three concentrations of standards for the drug product. During method application, six liquid hand sanitizer products were tested and all were determined to have ethanol or isopropanol above 70% v/v. Two liquid hand sanitizer products were determined to contain acetaldehyde as an impurity above the FDA recommended safety levels.

The use of a Quality by Design (QbD) approach in the development of pharmaceutical products is known to bring many advantages to the table, such as increased product and process knowledge, robust manufacturing processes, and regulatory flexibility regarding changes during the commercial phase. However, many companies still adhere to a more traditional pharmaceutical process development—in some cases due to the difficulty of going from a theoretical view of QbD to its actual application. This article presents a real-world case study for the development of an industrial pharmaceutical drug product (oral solid dosage form) using the QbD methodology, demonstrating the activities involved and the gains in obtaining systematic process and product knowledge.

Glycopeptide antimicrobials are a class of naturally occurring or semi-synthetic glycosylated products that have shown antibacterial activity against gram-positive organisms by inhibiting cell-wall synthesis. In most cases, these drugs are prepared in dry powder (lyophilized) form due to chemical and physical instability in aqueous solution; however, from an economic and practical point of view, liquid formulations are preferred. Researchers have recently found ways to formulate some glycopeptide antibiotic therapeutic drugs in aqueous solution at refrigerated or room temperature. Chemical degradation can be significantly slowed by formulating them at a defined pH with specific buffers, avoiding oxygen reactive species, and minimizing solvent exposure. Sugars, amino acids, polyols, and surfactants can reduce physical degradation by restricting glycopeptide mobility and reducing solvent interaction. This review focuses on recent studies on glycopeptide antibiotic drug stability in aqueous solution. It is organized into three sections: (i) glycopeptide antibiotic instability due to chemical and physical degradation, (ii) strategies to improve glycopeptide antibiotic stability in aqueous solution, and (iii) a survey of glycopeptide antibiotic drugs currently available in the market and their stability based on published literature and patents. Antimicrobial resistance deaths are expected to increase by 2050, making heat-stable glycopeptides in aqueous solution an important treatment option for multidrug-resistant and extensively drug-resistant pathogens. In conclusion, it should be possible to formulate heat stable glycopeptide drugs in aqueous solution by understanding the degradation mechanisms of this class of therapeutic drugs in greater detail, making them easily accessible to developing countries with a lack of cold chains.

Nobiletin (NOB), a polymethoxyflavonoid, is known for its antioxidant and anti-inflammatory effects and has antitumor activity. However, its poor solubility and low bioavailability pose a significant challenge in its delivery. In this experiment, NOB was added to Soluplus® (Sol)/l-ascorbyl 2,6-dipalmitate (ASC-DP) as a ternary system, and Sol/ASC-DP/NOB nanoparticles were obtained using the hydration method. The purpose of this study was to enhance the solubility of NOB, apply it for skin permeation, and improve antitumor activity. The preparation of Sol/ASC-DP/NOB nanoparticles was attempted using the hydration method, and particle size, zeta potential, and stability tests were performed to evaluate the formation of nanoparticles. 1H-1H NOESY/ROESY NMR spectral measurements were also performed to identify molecular interaction between NOB and Sol/ASC-DP. To evaluate its functionality, DPPH radical scavenging, skin permeation, fluorescence microscopy, and cell viability analyses were performed. The particles were approximately 100 nm in size in the ternary system (weight ratio (Sol/ASCDP/NOB=8/1/1)) and were relatively stable for approximately 7 days at 25 °C under light-shielded conditions. From the NMR spectrum measurements of Sol/ASCDP/NOB, a cross-peak was observed between the –OCH3 group: C6,8 (3.8 ppm) derived from NOB, the methyl group (2.0 ppm) derived from Sol, and the side chain portion (1.2 ppm) derived from ASC-DP. Cross-peaks were observed between the polyethylene glycol (PEG) backbone of Sol (3.6 ppm) and the side chain of ASC-DP (0.8–1.2 ppm). The formation of Sol/ASC-DP/NOB nanoparticles facilitated its skin permeation, and fluorescence microscopy confirmed improved permeation. The DPPH radical scavenging test revealed that Sol/ASC-DP/NOB had an IC50 of 46.7 μg/mL. Cell viability assays showed a 20–40% decrease in cell viability with the addition of Sol/ASC-DP/NOB at 0.1 mg/mL. Sol/ASC-DP/NOB nanoparticles were successfully prepared, and these were found to inhibit melanin formation and have antitumor activity.

This article describes in vitro and in vivo studies that aimed to further characterize the biopharmaceutical properties and pharmacokinetic (PK) profile of vericiguat and to guide dosing recommendations. Five open-label, phase I studies characterized the biopharmaceutical aspects of vericiguat, including absolute bioavailability, bioavailabilities of different formulations, dose proportionality, and food effect. Area under the curve (AUC) and maximum plasma concentrations (Cmax), determined by a noncompartmental analysis, were compared by analysis of variance, and a mixed-effects power model was used to assess dose proportionality. The effect of food on the dissolution of vericiguat was evaluated in vitro using media simulating the gastrointestinal tract under fed and fasted conditions. In vitro dissolution of intact vs crushed vericiguat tablet was assessed in quality control medium (HCl at pH 2), acetate buffer at pH 4.5, and phosphate buffer at pH 6.8. Dissolution of vericiguat increased under fed conditions. In healthy subjects, exposure (AUC and Cmax) increased ~ 40% with food vs fasted state (10 mg intact tablet) confirming a food effect on vericiguat bioavailability. Interindividual variability in exposure decreased ~ 20%, irrespective of meal type. Absolute bioavailability of vericiguat 10 mg (intact tablets, fed) was 93%. Vericiguat 2.5–10 mg demonstrated dose proportionality (intact tablets, fed) in healthy subjects. Dissolution studies showed no differences between the formulations, and this was confirmed with in vivo studies. Vericiguat tablets should be administered with food and may be crushed for patients who have difficulty swallowing.

The low solubility, weak acid drug, niclosamide is a host cell modulator with broad-spectrum anti-viral cell-activity against many viruses, including stopping the SARS-CoV-2 virus from infecting cells in cell culture. As a result, a simple universal nasal spray preventative was proposed and investigated in earlier work regarding the dissolution of niclosamide into simple buffers. However, starting with pharmaceutical grade, niclosamide represents a new 505(b)(2) application. The motivation for this second paper in the series was therefore to explore if and to what extent niclosamide could be extracted from commercially available and regulatory-approved niclosamide oral tablets that could serve as a preventative nasal spray and an early treatment oral/throat spray, with possibly more expeditious testing and regulatory approval. Measurements of supernatant niclosamide concentrations were made by calibrated UV-Vis for the dissolution of niclosamide from commercially available Yomesan crushed into a powder for dissolution into Tris Buffer (TB) solutions. Parameters tested were as follows: time (0–2 days), concentration (300 µM to -1 mM), pH (7.41 to 9.35), and anhydrous/hydrated state. Optical microscopy was used to view the morphologies of the initial crushed powder, and the dissolving and equilibrating undissolved excess particles to detect morphologic changes that might occur. Concentration dependence: Niclosamide was readily extracted from powdered Yomesan at pH 9.34 TB at starting Yomesan niclosamide equivalents concentrations of 300 µM, 600 µM, and 1 mM. Peak dissolved niclosamide supernatant concentrations of 264 µM, 216 µM, and 172 µM were achieved in 1 h, 1 h, and 3 h respectively. These peaks though were followed by a reduction in supernatant concentration to an average of 112.3 µM ± 28.4 µM after overnight stir on day 2. pH dependence: For nominal pHs of 7.41, 8.35, 8.85, and 9.35, peak niclosamide concentrations were 4 µM, 22.4 µM, 96.2 µM, and 215.8 µM, respectively. Similarly, the day 2 values all reduced to 3 µM, 12.9 µM, 35.1 µM, and 112.3 µM. A heat-treatment to 200 °C dehydrated the niclosamide and showed a high 3 h concentration (262 µM) and the least day-2 reduction (to 229 µM). This indicated that the presence, or formation during exposure to buffer, of lower solubility polymorphs was responsible for the reductions in total solubilities. These morphologic changes were confirmed by optical microscopy that showed initially featureless particulate-aggregates of niclosamide could grow multiple needle-shaped crystals and form needle masses, especially in the presence of Tris-buffered sodium chloride, where new red needles were rapidly made. Scale up: A scaled-up 1 L solution of niclosamide was made achieving 165 µM supernatant niclosamide in 3 h by dissolution of just one fifth (100 mg niclosamide) of a Yomesan tablet. These comprehensive results provide a guide as to how to utilize commercially available and approved tablets of niclosamide to generate aqueous niclosamide solutions from a simple dissolution protocol. As shown here, just one 4-tablet pack of Yomesan could readily make 165 L of a 20 µM niclosamide solution giving 16,500 10 mL bottles. One million bottles, from just 60 packs of Yomesan, would provide 100 million single spray doses for distribution to mitigate a host of respiratory infections as a universal preventative-nasal and early treatment oral/throat sprays throughout the world. pH dependence of niclosamide extraction from crushed Yomesan tablet material into Tris buffer (yellow-green in vial) and Tris-buffered saline solution (orange-red in vial). Initial anhydrous dissolution concentration is reduced by overnight stirring to likely monohydrate niclosamide; and is even lower if in TBSS forming new niclosamide sodium needle crystals grown from the original particles.

Random effects are often neglected when defining the control strategy for a biopharmaceutical process. In this article, we present a case study that highlights the importance of considering the variance introduced by random effects in the calculation of proven acceptable ranges (PAR), which form the basis of the control strategy. Linear mixed models were used to model relations between process parameters and critical quality attributes in a set of unit operations that comprises a typical biopharmaceutical manufacturing process. Fitting such models yields estimates of fixed and random effect sizes as well as random and residual variance components. To form PARs, tolerance intervals specific to mixed models were applied that incorporate the random effect contribution to variance. We compared standardized fixed and random effect sizes for each unit operation and CQA. The results show that the investigated random effect is not only significant but in some unit operations even larger than the average fixed effect. A comparison between ordinary least squares and mixed models tolerance intervals shows that neglecting the contribution of the random effect can result in PARs that are too optimistic. Uncontrollable effects such as week-to-week variability play a major role in process variability and can be modelled as a random effect. Following a workflow such as the one suggested in this article, random effects can be incorporated into a statistically sound control strategy, leading to lowered out of specification results and reduced patient risk.

Hydrolytic degradation of the polysorbate 20 (PS20) surfactant in protein-based liquid formulations releases free fatty acids (FFAs), which can accumulate to form particles in drug products during real-time (long-term) storage. To identify formulation conditions that mitigate the risk of particle formation, we conducted a longitudinal study using purified recombinant monoclonal antibody (mAb) formulated in 24 conditions. In this real-time stability study at 5 °C, three key formulation parameters—mAb concentration, initial PS20 concentration, and pH—were varied across representative ranges in a full-factorial design. A longitudinal regression analysis was used to evaluate the effects of these parameters and their interactions on PS20 degradation (via measurements of PS20, FFAs, and PS20 ester distribution) and on particle formation (via visible particle observations and subvisible particle counts). The time-dependent onset of visible particles trended with the rise in subvisible particle counts and FFA levels and fall in PS20 concentration. In the ranges studied here, lower mAb concentration and higher initial PS20 concentration delayed the onset of particles, whereas pH had a negligible effect. These observations were consistent with the general trends predicted by our previously published FFA solubility model. Taken together, these findings highlight the complex relationships between formulation parameters, PS20 degradation, and particle formation.

This conference report summarized a full-day workshop, “best practices for the development and fit-for-purpose validation of biomarker methods,” which was held prior to the American Association of Pharmaceutical Scientists (AAPS) PharmSci360 Congress, San Antonio, TX, November 2019. The purpose of the workshop was to bring together thought leaders in biomarker assay development in order to identify which assay parameters and key statistical measures need to be considered when developing a biomarker assay. A diverse group of more than 40 scientists participated in the workshop. The workshop and subsequent working dinner stimulated robust discussion. While a consensus on best practices was not achieved, some common themes and major points to consider for biomarker assay development have been identified and agreed on. The focus of this conference report is to summarize the presentations and discussions which occurred at the workshop. Biomarker assay validation is a complex and an evolving area with discussions ongoing.

Potassium chloride (KCl) syrup is widely used for the oral treatment of the hypokalemia. However, it is associated with unacceptable taste. In the present study, we sought to develop a palatable and easy to reconstitute KCl dry syrup as a commercially viable alternative to currently available KCl syrup. We explored the potential of Eudragit E100 as a taste-masking polymer to coat and improve the palatability of the KCl. With the help of fluid bed processor, KCl was coated with the solution containing varying amounts of Eudragit E100 (4, 6, 10 and 15%). Coating with 10% polymer solution enabled optimal fluid bed processing, higher entrapment of the KCl (81%) and better in vitro release profile in 0.1 N HCl and pH 6.8 phosphate buffer. A dry syrup formulation containing Eudragit E100 coated KCl with good physical and chemical stability in dry and reconstituted state was developed. The palatability of the optimized formulation and commercially available KCl syrup was evaluated using the Electronic Taste Sensing Machine. The developed formulation showed~ 2-fold better taste-masking compared to the commercial KCl syrup. Thus, present investigation describes the development of an effective alternative to the current KCl syrup that can offer better palatability, stability and patient compliance.