United States Pharmacopeia Research Articles

An Analytical Target Profile for the Development of an In Vitro Release Test Method and Apparatus Selection in the Case of Semisolid Topical Formulations.

This study focuses on how to define an Analytical Target Profile (ATP) which is intended for use in practice and on facilitating the selection of in vitro release test (IVRT) technology for diclofenac sodium topical hydrogel and cream. The implementation involves incorporating the new draft guidelines of the International Council for Harmonisation (ICH Q14) and USP (United States Pharmacopeia) Chapter 1220. Four IVRT apparatuses were compared (USP Apparatus II with immersion cell, USP Apparatus IV with semisolid adapter, static vertical diffusion cell, and a new, in-house-developed flow-through diffusion cell) with the help of the ATP. Performance characteristics such as accuracy, precision, cumulative amount released at the end of the IVRT experiment, and robustness were investigated. We found that the best apparatus for developing IVRT quality control (QC) tests in both cases was USP II with an immersion cell. All four different IVRT apparatuses were compared with each other and with the data found in the literature.

Comparison of In vitro Dissolution Tests of five brands of Diclofenac Sodium delayed release tablets in Moroccan market

This study aims to evaluate the similarity of in-vitro dissolution profiles, of commercially available generics of diclofenac sodium delayed-release tablets, of 25mg strength, with the innovator brand in Moroccan Market. Dissolution profiles for five brands were determined using the paddle method from the United States Pharmacopoeia. For the aptitude verification of the method, in our experimental conditions, linearity and accuracy tests were performed. The rate of dissolution was determined by Ultra-Violet Spectroscopy at 276nm. The assessment between the generics and the brand medicine was carried out under the similarity factor approach. We also presented an overview of the dissolution principles of tablet dosage form, and the pharmacopoeia dissolution test recommendations in our case. To compliance with US pharmacopoeia specifications, the rate of dissolution should be not more than 10% after 2hours in the acid stage, and not less than 75% at 45 minutes in the buffer stage. Furthermore, two dissolution profiles are considered similar when the f2 value is ≥50. According to routine quality control, evaluating the rate dissolution at the final point, all the generic medicines marketed in Morocco, meet the specification of the dissolution testing. However, using the comparison of dissolution profiles, only generic-2 is interchangeable with the innovator brand.

CRITICAL ANALYSIS OF POWDER FLOW BEHAVIOUR OF DIRECTLY COMPRESSIBLE COPROCESSED EXCIPIENTS

The aim of this pre-formulation study was to adopt simple linear regression modelling and correlation statistics to understand the associations between pharmacopoeial powder test methods using datasets generated from five commercial brands of directly compressible excipients with a specific focus to inferential implications in formulation design. Powder characterization was conducted using protocols defined in Chapter <1174> and <616> of the United States Pharmacopoeia (USP41-NF36). The study adopted a linear regression modelling analytics and correlation statistics using the fitting algorithm of OriginPro® (OriginPro, Version 2021b, OriginLab Corporation, Northampton, MA, USA). In the results, the modulus of Pearson’s product moment correlation coefficient was used to measure the strength of the linear association between test variables and a correlation matrix generated. Strong positive correlation modulus of Hausner’s Ratio (HR) with Carr’s index (r=+0.999) and static angle of repose (r=+0.932) were evident. Bulk density strongly correlates with tap density in the positive direction (r=+0.911). Tap density also shows a slight negative correlation with HR (r=-0.230), Carr’s index (r=-0.228), and static angle of repose (r==-0.421), while Carr’s index strongly correlated with static angle of repose (r=+0.933). In conclusion, modelling bivariate powder flow datasets has provided a powerful but simplistic statistical relationship for characterizing the modulus of association between HR, Carr’s index, and static angle of repose of the model excipients useful in preformulation design of pharmaceutical formulations.

Exploration of surface tension measurement methods for pharmaceutical excipients

Surface tension is a crucial functional indicator for various classes of pharmaceutical excipients, as highlighted in both the Pharmacopoeia of the People’s Republic of China (ChP) < 9601 Guidelines for Functionality-related Characteristics of Pharmaceutical Excipients > and the United States Pharmacopoeia (USP) < 1059 Excipient Performance >. However, there are few systematic studies on surface tension measurement of pharmaceutical excipients, resulting in a lack of stable parameter support in practical applications. In this study, we aim to fill this gap by exploring three different methods for measuring surface tension. These methods were carefully developed taking into account the actual measurement process and statistical theory, thus ensuring their applicability and reliability. Through comparative analyses, we have identified the most suitable measurement methods for different classes of pharmaceutical excipients. In addition, this paper describes the surface adsorption behavior of various excipients. Therefore, this study provides valuable guidance for the determination of surface tension and the study of surface adsorption behavior, which lays the foundation for further comprehensive research in the field of surface tension of pharmaceutical excipients and the improvement of general pharmacopoeia specification.

A Review of Probiotic Ingredient Safety Supporting Monograph Development Conducted by the United States Pharmacopeia (USP)

The United States Pharmacopeia (USP) is an independent, nonprofit science-based organization whose mission is to improve global health through public standards and related products for medicines, food and dietary supplements. Probiotic-based dietary supplements are increasingly popular in the marketplace and USP has developed fourteen monographs specific to probiotic ingredients, including representatives from the Genera Lactobacillus, Bacillus, Streptococcus, and Bifidobacterium. These monographs include the definition of the article, tests for identification, quantification assays (enumeration in the case of probiotics), limits for contaminants, and other quality parameters when appropriate. In addition to quality, the USP also considers the safety of probiotics for monograph development. This report includes an overview of the USP admission evaluation process for probiotics as well as a tabular summary of the probiotic monographs currently available. Pharmacopeia monographs can guide manufacturers and brand owners and protect consumers through establishment of quality standards.

Determination of omeprazole via fluorescence-quenching methodology; application to content uniformity testing.

A new, proven, economical spectrofluorimetric approach has been used to determine the proton pump inhibitor omeprazole (OMP). This innovative technique is based on the ability of OMP to quench the native fluorescence of the mercurochrome dye in an acidic (pH3.6) solution. Because it was discovered that quenching is proportional to the drug concentration, this dye was used as a sensor for OMP detection. The fluorescence intensity was measured at 518/540 nm, and its linear response ranged from 0.2-10.0μg/mL with a linear coefficient of 0.9999. The computation yielded a limit of quantification (LOQ) of 0.20 μg/mL and a limit of detection (LOD) of 0.07 μg/mL. Every circumstance and element impacting the reaction product was examined in detail. Pharmacopeial standards carried out the validation. The approved method investigated several commercial preparations and formulations, and the results were favorably compared with those provided by a reference method. According to United States Pharmacopeia (USP) rules, content consistency for two distinct formulations was evaluated.

Disintegration testing for orally disintegrating tablets (ODTs): An overview

Prescribing orally disintegrating tablet (ODT) dosage form is a common practice. For several populations, including geriatrics and pediatrics, ODTs are one of the most desired dosage forms. They are solid dosage forms designed to disintegrate or dissolve very quickly in contact with saliva as soon as they are placed in oral cavity of a patient. According to United States Pharmacopeia (USP), every dosage form has to pass some quality control tests to ensure uniformity and performance of this dosage form. For ODTs, disintegration test is fundamental to ascertain time required for tablets to break down and release their contents for dissolution and absorption. Additionally, it is a crucial predictive test for determining in vitro/in vivo association. There are no mandatory universal disintegration testing standards for ODTs, however, as stated in the USP. Instead, recent USP refers to individual manufacturer monograph specifications which may vary from one monograph to another. This article discusses several developed disintegration tests and methods for ODTs such as OD-mate testing, basket rack assembly, CCD camera, texture analyzer (TA), special disintegration equipment, prototype disintegration tester (PDT), simple approach, and modified wetting test and elaborates on their advantages and disadvantages.

A new ultrasound-assisted microextraction for elemental impurities determination in tablets by ICP-MS according to USP chapters 232 and 233

Along with the United States Pharmacopeia (USP) chapters 232 and 233 regarding elemental impurities in pharmaceutical products, new challenges have been imposed in terms of sample preparation procedures prior to inductively coupled plasma mass spectrometry analysis, considering the matrix complexities. As so, a new microextraction procedure assisted by ultrasound using a cup-horn sonoreactor, minimal reactants, and sample was proposed and validated according to USP. The procedure was optimized with samples of milled tablets and 3 different acid mixtures (HNO3, 3HNO3:1HCl, and 9HNO3:1HF) and it was compared with microwave-assisted acid digestion. In the validation step, recoveries ranging from 85 to 120 % and RSD below 10 % were obtained for 22 analytes (except Ag and Pt) with satisfactory linearity and good sensitivity. The method was then applied for 37 samples of antidepressants, which presented trace levels of As, Ba, Cd, Co, Cr, Cu, Ni, Pb, Pd, Sn, and V.

Development of a method to assess the dissolution of soft gelatin capsules containing progesterone in oily suspension

Progesterone is a class II active pharmaceutical ingredient according to the biopharmaceutics classification system, so its absorption is affected by solubility and dissolution rate. The work aimed to develop a dissolution method applicable to soft gelatin capsules of 100 and 200 mg of progesterone. Sink conditions were established based on solubility studies; the dissolution apparatus was selected, and the operational conditions of the method were established using an experimental statistical design. The established conditions were challenged in progesterone products, for which their result was already known from in vivo studies, with the same formulation but different particle size, to evaluate the discriminatory power of the method. The dissolution conditions selected were: United States pharmacopoeia apparatus 3, speed of 30 deeps per minute, dissolution media of 250 ml phosphate buffer solution at pH 6.8 with 4% sodium lauryl sulfate, 30 and 40 mesh at the top and bottom of the cell, respectively, and using a sinker for each capsule evaluated. The method proved to be discriminatory for the formulations studied. In addition to being functional for the evaluation of progesterone release at the product development stage, this method is also useful as a product quality control test.

Potency and Powder X-ray Diffraction (PXRD) Evaluation of Levothyroxine Sodium Tablets under Ambient, Accelerated, and Stressed Conditions.

Levothyroxine tablets, although highly prescribed in the United States, have been one of the most frequently recalled products. Because of the importance of the medication, several efforts have been put in place by the United States Food and Drug Administration (US FDA) to control the quality of levothyroxine tablets available to patients using the drug. The choice of excipients used in the formulation has been shown to impact the hygroscopicity and microenvironment, and ultimately the stability of the levothyroxine tablets formulations. Based on information generated from the US FDA Enforcement Report database, one of the main reasons for recalls is the low potency of different batches of the product. The yearly product recall trends for levothyroxine formulations were determined using the FDA Enforcement Report database. Three brands of levothyroxine tablets were selected with excipient lists similar to those products that have been historically recalled. The samples were placed at ambient (~23 °C), accelerated stability (40 °C/75% RH), and stress (50 °C/75% RH) conditions for up to 6 months. Sample potencies were determined at 0, 1.5, 3, and 6 months using the methods for assay and impurities in the United States Pharmacopeia (USP) monograph for levothyroxine tablets. Additional sample monitoring was conducted by overlaying the initial powder X-ray diffractograms (PXRD) of the samples from 0 months with the patterns generated thereafter. There has been a decline in the number of levothyroxine tablets recalled over the years. The highest numbers of recalls were recorded in the years 2013 [33] and 2020 [23]; no recalls occurred in the years 2019 and 2022. All of the brands evaluated met the USP 95.0-105.0% assay requirements at 1.5 months under accelerated conditions; only one of the brands complied at 3 months. Under ambient conditions, two brands were stable at 6 months, with borderline assay results. For stability, levothyroxine was found in microgram quantities in the formulations and PXRD could not detect changes at these low levels. However, we found some distinguishing data for samples under stress conditions.

Preconcentration and measurement of trace Amitriptyline hydrochloride in water samples using magnetic nanoparticles with dispersive solid‐phase extraction

AbstractIn the separation and determination of trace amounts of drugs in aqueous samples, there is a major challenge in synthesizing highly efficient, cost‐effective, and easy‐to‐use adsorbents based on natural polymers, which are also biocompatible and biodegradable. In the proposed method, magnetite nanoparticles (Fe3O4) on chitosan (as the carrier) modified with β‐cyclodextrin (BCD) were used as a suitable adsorbent for the pre‐concentration and solid‐phase extraction of trace amounts of Amitriptyline HCl (hydrochloride). Ultraviolet spectrophotometer (λ = 236 nm) was the main instrument used for analyte detection and quantification. Moreover, X‐ray diffraction, Fourier transform infrared spectroscopy, Field Emission Scanning Electron Microscopy, and Energy‐Dispersive X‐ray were used for the identification and characterization of the structure and morphology of the adsorbent and to establish the formation of the synthesized magnetic nanosorbents, as well as to confirm the analyte binding to the adsorbent. Experimental variables affecting the extraction/pre‐concentration and determination of the analyte were investigated and optimized; pH of the sample solution, the amount of NaCl salt (in terms of ionic strength of the solution), the amount of adsorbent, temperature, adsorption time, and volume of the eluent (methanol) were the optimized parameters. Finally, the method was successfully applied for the determination of spiked Amitriptyline hydrochloride (HCl) in tap water and human urine samples. Also, High‐Performance Liquid Chromatography was performed on the aqueous samples to compare the proposed method with the USP (the United States Pharmacopeia) standard method of Amitriptyline HCl assay and after performing a t‐test (confidence level of 95%), no significant difference was observed between the two methods. High accuracy and precision (RSD = 3.91%), High analysis speed, few limitations, low expenses, pure extracted analyte, and low waste were the advantages of this method. This method was also compatible with many existing device methods. Under the optimized experimental conditions, the calibration graph was linear in the range of 0.183 to 50 mg.L−1 with a correlation coefficient of 0.996. RSD of the method was 3.91%, the limit of detection was 37.8 µg.L−1, the maximum sorption capacity of the adsorbent for Amitriptyline hydrochloride was 306.525 mg.g−1 and the preconcentration factor was 3.61. Eventually, the proposed method was compared to other methods that have been performed for the determination of Amitriptyline hydrochloride.

Monograph on the Use of Herbs to Address Metabolic Syndrome

IntroductionMetabolic syndrome is a collection of symptoms that have become an issue on a global scale. While allopathic medicine can address the downstream symptoms, the metabolic pathways that are the root cause of the syndrome can be managed using herbs. MethodsCriteria for the syndrome were set by the World Health Organization. Suggested herbs are taken from World Health Organization monographs, the British Pharmacopoeia, the United States Pharmacopoeia and the National Formulary, the Ayurvedic Pharmacopoeia, the Pharmacopoeia of the People's Republic of China, and the Japanese Pharmacopoeia. Herbs are cross-referenced with the primary literature when possible. Dietary recommendations and supplements are mentioned tangentially; however, they are not the intended focus of this monograph. ResultsHyperglycemia is considered a principal component and driver of metabolic syndrome. Insulin resistance, glycolysis, and insulin production can all be affected by herbs. Lipid metabolism occurs primarily in the liver; liver function can be enhanced using herbs. Inflammation caused by a hyperglycemic state can also be managed using herbs and reduced the progression of associated diseases. Since glycolysis and energy production occur in the mitochondria, supporting mitochondrial health with herbs is critical to positively affecting metabolic syndrome. ConclusionsBy using herbs to manage hyperglycemia, inflammation, liver congestion, and mitochondrial health, metabolic syndrome can be slowed, stopped, or even reversed.

Harmonizing international quality standards for Andrographis paniculata: A comparative analysis of content determination methods across pharmacopeias

The quality standards for Andrographis paniculata, a widely used medicinal herb, exhibited significant variations across different pharmacopeias. In this study, we compared the HPLC content determination methods and total lactone content of A. paniculata samples from different regions, as specified in the Chinese (CP), United States (USP), European (EP), Thai (TP), and Indian pharmacopeias (IP), as well as the Hong Kong Chinese Materia Medica Standards (HK). We aimed to assess the differences and similarities among these pharmacopeias and harmonized international quality standards for A. paniculata. The analysis revealed variations in sample preparation, liquid chromatographic conditions, fingerprint profiles, and total lactone content among the different pharmacopeias. Specifically, the CP and HK methods exhibited superior sample preparation and chromatographic separation. Further comparing the content of 20 A. paniculata samples with the CP, USP, EP and HK methods showed consistent determinations for the same components, indicating similar detection capabilities. The discrepancies in total lactone content primarily stemmed from differences in the number and types of detected compounds. Moreover, the acceptance criteria exhibited a stringency in the order CP > HK > EP > USP. In conclusion, this comparison analysis of content determination in CP, USP, HK, EP, TP and IP provided a scientific foundation for the international standardization and trade regulations of A. paniculata. It also served as a valuable reference for the development of international quality standards for other medicinal herbs, facilitating the harmonization of global pharmaceutical standards.

DETERMINATION OF TOXIC HEAVY METALS IN CHOLIC ACID USING QUADRUPOLE INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY

Objective: The information on the presence of toxic heavy metals in pharmaceutical starting materials and finished product is very crucial from the viewpoint of human life and its hazardous impact on the worldwide environment. The present work deals with the detailed quantification of the toxic heavy metals, namely, V, Co, Ni, Cd, Hg, Pb, and As, present in colic acid using quadrupole inductively coupled plasma mass spectrometry (Q-ICPMS) with prior microwave-assisted digestion. Moreover, the preliminary characterization of commercially available cholic acid by FT-IR, NMR (1H and 13C), SEM-EDAX has also been carried out. Methods: Cholic acid of synthesis grade, Nitric acid (65%) AR. grade, ethylene diamine tetra acetic acid sodium salt AR grade, and certified reference metal stock standard solutions (1000 mg/L) of multiple elements prepared in 2–3% HNO3 of analytical grade were purchased from Merck (Darmstadt, Germany). All the samples were treated with nitric acid and microwave-assisted digestion. For the accurate determination of the elemental amount, various digested solutions and post-digestion diluents were tested. The linearity, accuracy, precision, limit of detection (LOD), and limit of quantification (LOQ) of the analytical technique were evaluated in accordance with the United States Pharmacopoeia 233 standard. Results and Discussion: The Q-ICPMS-based analytical method was validated for specificity, LOD, LOQ, linearity, accuracy, precision, and uncertainty. The estimated detection limits of the toxic heavy metals in cholic acid were in the range 2–180 μg/L. The quantification limits were in the range of 1.5–60 μg/L. Mean recoveries±standard deviations at different spiking levels were in the range 75.3±2.1–104.9±8.5%. The coefficients of variation were in the range of 0.5–8.1%. Conclusion: The precision of the analytical method, in terms of relative standard deviation, was below 1.95%. The uncertainty in the quantification of all the validated elements was found to be ≤1.70% for Sample 1.

DETERMINATION OF TOXIC HEAVY METALS IN CHOLIC ACID USING QUADRUPOLE INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY

Objective: The information on the presence of toxic heavy metals in pharmaceutical starting materials and finished product is very crucial from the viewpoint of human life and its hazardous impact on the worldwide environment. The present work deals with the detailed quantification of the toxic heavy metals, namely, V, Co, Ni, Cd, Hg, Pb, and As, present in colic acid using quadrupole inductively coupled plasma mass spectrometry (Q-ICPMS) with prior microwave-assisted digestion. Moreover, the preliminary characterization of commercially available cholic acid by FT-IR, NMR (1H and 13C), SEM-EDAX has also been carried out. Methods: Cholic acid of synthesis grade, Nitric acid (65%) AR. grade, ethylene diamine tetra acetic acid sodium salt AR grade, and certified reference metal stock standard solutions (1000 mg/L) of multiple elements prepared in 2–3% HNO3 of analytical grade were purchased from Merck (Darmstadt, Germany). All the samples were treated with nitric acid and microwave-assisted digestion. For the accurate determination of the elemental amount, various digested solutions and post-digestion diluents were tested. The linearity, accuracy, precision, limit of detection (LOD), and limit of quantification (LOQ) of the analytical technique were evaluated in accordance with the United States Pharmacopoeia 233 standard. Results and Discussion: The Q-ICPMS-based analytical method was validated for specificity, LOD, LOQ, linearity, accuracy, precision, and uncertainty. The estimated detection limits of the toxic heavy metals in cholic acid were in the range 2–180 μg/L. The quantification limits were in the range of 1.5–60 μg/L. Mean recoveries±standard deviations at different spiking levels were in the range 75.3±2.1–104.9±8.5%. The coefficients of variation were in the range of 0.5–8.1%. Conclusion: The precision of the analytical method, in terms of relative standard deviation, was below 1.95%. The uncertainty in the quantification of all the validated elements was found to be ≤1.70% for Sample 1.

Antimicrobial Effectiveness Testing of Resorbable Electrospun Fiber Matrix per United States Pharmacopeia (USP) .

Contamination of surgical, traumatic, and chronic wounds with microorganisms presents a challenge to successful wound healing. In the present in vitro study, a syntheticelectrospun fiber matrix (SEFM) cleared for use in the management of chronic, surgical, and traumatic wounds underwent USP (United States Pharmacopeia) <51> Antimicrobial Effectiveness Testing to determine its in vitro effectiveness against various microorganisms commonly found in non-healing wounds. The SEFM was tested in both sheet (s-SEFM) and micronized form (m-SEFM) againstEscherichia coli, Pseudomonas aeruginosa,Staphylococcus aureus,Aspergillus brasiliensis,Candida albicans,Proteus mirabilis, andEnterococcus faecalis. Testing was performed per the USP <51> standard on days 7, 14, and 28. Both the s-SEFM and m-SEFM met the USP <51> acceptance criteria for all microorganisms. The results obtained for s-SEFM demonstrated >1-log10reduction againstE. coli, S. aureus, P. aeruginosa, P. mirabilis, E. faecalis,andC. albicansat day 7; >3-log10reduction with no detection of these microbes at days 14 and 28, and no increase from initial inoculum at days 7, 14, and 28 againstA. brasiliensis.The results obtained for m-SEFM demonstrated >3-log10reduction with no detectable microorganisms at day 7. The results observed in this study indicate that the SEFM is effective in vitro at inhibiting bacterial and fungalgrowth and colonization per USP <51> testing.

Comprehension of pharmaceutical pictograms in sub-Saharan migrants newly arriving in Europe: An exploratory study

BackgroundMigratory pressure from sub-Saharan Africa on Europe must also be addressed from a health literacy perspective. Sub-Saharan migrants newly arriving in Europe generally have lower literacy skills compared to the host community's citizens and special learning needs. Pictograms give health professionals a means of communicating medication instructions to people with no common language or who are illiterate, or both. ObjectiveThis work aimed to explore the comprehension of a set of United States Pharmacopoeia (USP) pictograms by sub-Saharan migrants newly arriving in Europe. MethodsA quantitative cross-sectional study was carried out. A voluntary survey was conducted among a population ≥ 18 years of age in a Temporary Stay Centre for Immigrants located in the Spanish city of Melilla (North Africa) in June 2022. The form included a selection of 10 USP pictograms to assess their comprehension. According to the International Organization for Standardization, a pictogram must receive 66.70% correct answers to be acceptable. ResultsFifty-one sub-Saharan immigrants participated in this study. None of the pictograms reached comprehensibility threshold. ConclusionPharmaceutical pictograms are ineffective in practice when they are not designed in a culturally sensitive manner.

A historical review of early Sino-American communication in Chinese materia medica: Three historical events from the 17th century to 1848

The early period of Sino-American communication in Chinese materia medica referred to the historical period from the 17th century, European trade overseas and the frequent communication of missionaries, to 1848 when gold prospectors from China travelled to America. This paper reviewed and examined the three historical events in this period : the spread, trade, and introduction of tea; the first edition of the United States Pharmacopoeia and its collection of Chinese medicines and preparations; and the discovery and trade of American ginseng hoping to explore the basic historical facts of the spread and exchange of Chinese medicine between China and America in the early period. The paper explored these historical factors, provided effective references for developing cooperation in public health between China and America and the start of the constructing of a Global Community of Health for All.

Influence of polymers on oxaprozin dissolution kinetics and mechanisms

In this work, the influences of polymers (HPMC E3, PEG 6000, PVP K25, PVP K30), temperature, stirring speed and polymer mass fraction on the oxaprozin (OXA) dissolution profiles were measured by a United States Pharmacopeia (USP) Ⅱ dissolution apparatus. The two-step chemical potential gradient model combined with the interfacial steady-state mass transfer model as well as PC-SAFT (perturbed-chain statistical associating fluid theory) were used to analyze the dissolution mechanism of OXA under different conditions. The presence of polymer could promote the surface reaction of OXA while temperature and stirring speed have different influences on the surface reaction and diffusion. The diffusion boundary layer thickness δ of OXA tablets increases with the increase of temperature and decreases with the increase of stirring speed. Based on the obtained surface reaction rate constant ks and diffusion rate constant kd, the dissolution profiles with high accuracy compared with the experimental data.

Dapsone determination in tablets to leprosy treatment using a portable NIR spectrometer

Leprosy is a neglected disease with limited technological advancements in the development of new formulations and analytical methods. The pharmaceutical industry offers several analytical alternatives for drug quality control; however, they are expensive, environmentally harmful, and labor-intensive. To address this, the United States Pharmacopoeia recommends the use of high-performance liquid chromatography (HPLC). In such a context, there arises a need for eco-friendly analytical approaches, such as near-infrared (NIR) spectroscopy, which offers the advantages of being non-destructive and eliminating the need for chemicals and solvents. Thus, in this study, we initially developed and validated an HPLC method for the quantification of dapsone in tablets. The method demonstrated selectivity, linearity, precision, accuracy, and very low limits of detection and quantification. Subsequently, the dapsone contents determined by HPLC in manipulated and industrial tablets were used as reference values to construct chemometric models based on NIR spectra acquired using a portable device. Partial Least Squares (PLS) and the Successive Projections Algorithm for interval selection coupled with PLS (iSPA-PLS) were then employed. Only the models constructed with linear baseline-corrected (LBC) spectra yielded significant results, with a ratio of performance to deviation (RPD) higher than 3. LBC/iSPA-PLS was the best model, selecting 3 out of 5 divided intervals, incorporated analytical information related to the aromatic rings and amino groups present in the dapsone molecule. This model achieved a relative prediction error of only 2.78 and 2.54 % for both the manufactured and industrialized tablets, respectively, and a limit of detection of 5.38 mg per 100 g of tablet. Therefore, the proposed methodology can be hereafter applied to the quality control of dapsone tablets, even in the presence of non-modeled excipients.