States Pharmacopeia Research Articles

Considerations for developing a health-system 503B outsourcing strategy.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. To provide guidance for health systems on how to develop a strategy for utilizing 503B outsourcing facilities for sterile product preparation. Health-system pharmacies face an increasingly complex set of challenges related to providing sterile products to patients. New United States Pharmacopeia <797> regulations, increasing drug shortages, and an ongoing pharmacy technician workforce shortage have made sterile compounding more difficult than ever for health-system pharmacies. Outsourcing of production to 503B outsourcing facilities is one strategy pharmacy leaders can use to help navigate these challenges. However, there are many factors to consider when deciding whether to outsource a product and which 503B vendors are safe and reliable. The Cleveland Clinic Health System (CCHS) has developed a robust internal structure to appropriately vet 503B outsourcing facilities for safety and reliability, as well as standardized criteria used to determine which products will be outsourced. This article describes the tools CCHS has used to evaluate 503B outsourcing vendors and to evaluate individual products to determine the pros and cons of outsourcing vs insourcing. Additionally, general considerations regarding outsourcing are described. Outsourcing to 503B facilities can be an effective strategy for navigating sterile compounding challenges but is not without some risk. Pharmacy leaders must develop a standardized approach to thoroughly evaluate 503B vendors and products to ensure their outsourcing strategy is both safe and cost-effective.

A Novel Method for Development and Validation of the Degradation Products Analysis of N-Carbamylglutamate with UHPLC by Using Design of Experiment Approach.

Carglumic acid, also known as N-carbamyl-l-glutamic acid, is a medication used in the treatment of a rare genetic disorder called N-acetylglutamate synthase (NAGS) deficiency. To the authors' knowledge, there was no method reported in the literature for the determination of degradation products suitable for quality control analyses of carglumic acid. Thus, the aim of the presented study is to develop an impurity method with a UHPLC/DAD detector configuration compatible with industrial standards from the European Pharmacopeia and the United States Pharmacopeia, making the drug more accessible for developing and underdeveloped countries through its precise evaluation. The method involved the separation of carglumic acid and its degradation products using a reverse-phase C18 column (Waters, BEH 150 mm × 2.1 mm, 1.7 μm) at a flow rate of 0.39 mL/min with a stop time of 10 min. To separate all unknown and known impurities, a gradient elution (phosphate buffer, pH 2.4, and acetonitrile) system was used. The detection was performed at 214 nm. Forced degradation studies were conducted under different stress conditions, including acidic, basic, oxidative, thermal, and photolytic stress. Placket-Burman statistical experimental design was used to demonstrate the robustness of this method, and the suitability of the method was confirmed under the applied conditions. Box-Behnken design was used to provide the optimum resolution between the peaks determined to be critical during the optimization. The developed method was validated according to ICH guidelines for specificity, linearity, accuracy, precision, and robustness. The limit of detection and limit of quantification were 0.7 and 0.15 μg/mL for carglumic acid, respectively.

Comparative Analysis of Taper Point and Reverse Cutting Needles on Skin Puncture Force.

Reverse cutting needles are commonly used in cutaneous surgery due to their perceived ease of use. Despite this, there is limited research evaluating the force required to puncture skin using contemporary needles. This study aims to compare the puncture forces required for two different needle geometries across various gauge sizes. The authors assessed the force necessary to penetrate samples of human abdominal skin samples using taper needles of three different United States Pharmacopeia gauge sizes with their respective reverse cutting needle counterparts. Taper point needles tested were RB-1 (3-0), TF (4-0), and C-1 (5-0), while reverse cutting needles included PS-2 (3-0) and P-3 (4-0, 5-0). An electronic force meter was used to record the puncture force required by each needle type. The mean puncture force in newtons (N) for taper point needles was 1.00, 0.74, and 0.48 for RB-1, TF, and C-1, respectively. The mean puncture force for reverse cutting needles was 0.95 N, 0.60 N, and 0.51 N for PS-2, P-3 (4-0), and P-3 (5-0), respectively. There was a direct relationship between needle body diameter and puncture force for both needle geometries. There was no clinically significant difference in skin puncture force between needle geometries.

Development of a new inversion-voltammetric technique in determining inorganic iodine in Laminariae thalli L. for the quality control of raw materials in factory laboratories

Objectives. To develop and validate a methodology for determining inorganic iodine in Laminariae thalli L., corresponding to the norms of the State Pharmacopoeia of the Russian Federation, 15th edition (SPh 15). The methodology needs to be valid and suitable for the quality control of pharmaceutical raw materials in factory laboratories.Methods. Cathode inversion voltammetry was used as an instrumental method for determining inorganic iodine using a graphite electrode capable of sorbing electroactive ion associates of surfactant–iodine.Results. When compared with the titrimetric technique recommended by SPh 15, the proposed technique is more selective, sensitive and less time-consuming. The efficiency and metrological characteristics of the technique were confirmed by validation in accordance with the requirements of SPh 15.Conclusion. The paper presents a new method for determining the gross content of inorganic iodine in Laminariae thalli L. This technique can be used not only in scientific research, but also in the routine quality control of medicinal plant raw materials in control and analytical laboratories engaged in pharmaceutical quality control.

The Impact of a Non-Pathogenic Strain of Fusarium Oxysporum on Structural and Biochemical Properties of Flax Suspension Cultures.

Flax (Linum usitatissimum L.) is an important crop plant with pharmaceutical significance. It is described in pharmacopoeias (the United States Pharmacopeia and the European Pharmacopoeia), which confirms that it (especially the seeds) is a valuable medicinal product. Similar to flax seeds, which accumulate bioactive compounds, flax in vitro cultures are also a rich source of flavonoids, phenolics, lignans and neolignans. In the present study, flax suspension cultures after treatment of the non-pathogenic Fusarium oxysporum strain Fo47 were established and analyzed. The study examined the suitability of Fo47 as an elicitor in flax suspension cultures and provided interesting data on the impact of these endophytic fungi on plant metabolism and physiology. Two flax cultivars (Bukoz and Nike) and two compositions of media for flax callus liquid cultures were tested. Biochemical analysis revealed enhanced levels of secondary metabolites (total flavonoid and total phenolic content) and photosynthetically active pigments in the flax callus cultures after treatment with the non-pathogenic fungal strain F. oxysporum Fo47 when compared to control, untreated cultures. In cultures with the selected, optimized conditions, FTIR analysis was performed and revealed changes in the structural properties of cell wall polymers after elicitation of cultures with F. oxysporum Fo47. The plant cell wall polymers were more strongly bound, and the crystallinity index (Icr) of cellulose was higher than in control, untreated samples. However, lignin and pectin levels were lower in the flax callus liquid cultures treated with the non-pathogenic strain of Fusarium when compared to the untreated control. The potential application of the non-pathogenic strain of F. oxysporum for enhancing the synthesis of desired secondary metabolites in plant tissue cultures is discussed.

Current and Future Pharmacopoeial Requirements for the Quality of Extemporaneous Medicinal Products: A Review of Regulatory Standards

INTRODUCTION. The organisation of extemporaneous compounding in pharmacies is currently considered to be a priority for the national healthcare system. Extemporaneous medicinal products used by patients should meet high quality, safety, and efficacy standards. Provision of consistent and science-based requirements for the quality of medicines, particularly those compounded in pharmacies, is a key area of concern for standardisation.AIM. This study aimed to analyse international experience and determine areas for the improvement of standardisation approaches of the State Pharmacopoeia of the Russian Federation to the quality of medicinal products compounded in pharmacies.DISCUSSION. The study investigated the common and distinctive properties of extemporaneous preparations compounded in pharmacies (and not subject to registration) and medicinal products manufactured by pharmaceutical companies. The authors analysed the requirements and recommendations for compounding and quality assurance of extemporaneous medicinal products provided by the regulatory and pharmacopoeial authorities of the Russian Federation, the Republic of Belarus, the European Union, the United Kingdom, the USA, and Canada. The United States Pharmacopeia includes circa 150 individual monographs for non-sterile compounded drug products with particular compositions and over 20 individual monographs for sterile compounded drug products. The European Pharmacopoeia requires that extemporaneous preparation should be organised within the quality assurance framework of a pharmacy after a proper risk assessment. In the Republic of Belarus, extemporaneous medicinal products are compounded in line with the requirements of the Good Compounding Practices and the State Pharmacopoeia of the Republic of Belarus, which provide rapid testing procedures for extemporaneous medicinal products.CONCLUSIONS. The study identified the following areas for the development of requirements for the quality of medicinal products compounded in pharmacies: the determination of rapid testing approaches; the development of pharmacopoeial monographs for active pharmaceutical substances used in extemporaneous compounding, with the Identification section supplemented with an additional subsection on pharmacy-specific analytical procedures; and the development of pharmacopoeial monographs for frequently used compounding formulae.

Analysis of US Marketed Artemisinin Supplements for Use in Dogs.

Oral artemisinin has antiparasitic activity and may help improve treatment success rates in dogs infected with Babesia gibsoni. However, these artemisinin products are unapproved and unregulated botanical supplements. They have not been evaluated for safety and efficacy or for strength, purity, or quality compared with a reference standard. Before considering these products for a clinical study, we evaluated the strength of four suppliers of artemisinin capsules using an high-performance liquid chromatography method validated in our laboratory. We found that the four artemisinin-labeled products that were tested had high within product and between product variability in capsule strength compared with the stated capsule strength on the product label. No products met the acceptance criteria of the United States Pharmacopeia and International Council for Harmonisation (ICH) as well as the criteria adapted by the authors. One product had no detectable artemisinin, and the other three products were much higher than the stated label strength. The results of this study reinforce the importance of testing unapproved and unregulated supplements before recommending a supplement for clinical use in dogs.

Quality evaluation of selected expired fluoroquinolones medicines obtained from the public hospitals in Jimma zone, Oromia regional state, Ethiopia.

The problem of medicine expiration presents a notable obstacle, resulting in considerable financial losses. Nevertheless, there is currently limited data indicating that certain medications do not experience a significant decrease in effectiveness after their expiration date. Therefore, the aim of the study was to assess the physico-chemical quality of expired fluoroquinolone antibiotics. The expired samples of fluoroquinolone antibiotics were purposively collected from public hospitals in the Jimma zone of the Oromia regional state, Ethiopia. A World Health Organization quality evaluation sampling strategy was employed. Then, simple random sampling techniques were utilized for the selection of tablets for the laboratory quality control test. The assay, identification, and dissolution were performed in accordance with the United States Pharmacopeia (USP) guidelines, as well as failure mode and effect analysis (FMEA) techniques. The finding revealed that about 100% (7/7) expired samples passed pharmacopeia quality specifications for identity and assay tests. However, of the seven expired brands, about 14.3% (1/7) of the sample (Code-002) was unable to release its API content within the USP criteria of 30 min. The risk-based quality evaluation revealed that assay was the most critical quality attributed to ciprofloxacin tablets (RPN = 189), followed by identity (RPN = 100). Assay was also the most critical quality attribute (RPN = 378), followed by identity (RPN = 100) for Norfloxacin tablets. The risk-based desirability function approach showed that 75% (3/4) of ciprofloxacin products were of good quality, and 25% (1) were found to be of acceptable quality, while the desirability function of norfloxacin tablets was found to be excellent 1 (33.3%), good 1 (33.3%), and acceptable 1 (33.3%). The study revealed that medications can maintain their quality beyond their labeled expiration date. By combining pharmacopeial standards with risk-based approaches like failure mode and effect analysis (FMEA), the study provides a comprehensive evaluation framework. This approach not only confirms the continued effectiveness of expired fluoroquinolone antibiotics but also underscores the potential waste reduction and cost-saving benefits. This could significantly contribute to addressing healthcare challenges in low-resource settings, promoting more efficient pharmaceutical resource utilization.

Development, Optimization, and Validation of an in vitro Cell-Based Bioassay to Determine the Biological Activity of Teriparatide (PTH1–34)

AbstractThis study aimed to establish an efficient in vitro cell-based assay to measure the activity of teriparatide (PTH1–34). In this study, a rat osteosarcoma cell line (UMR-106) was treated with various concentrations of PTH1–34, and the biological activity of PTH1–34 was determined by quantitatively measuring intracellular cyclic adenosine monophosphate levels using a time-resolved fluoroimmunoassay. A four-parameter fitting analysis was used to calculate the relative potency of the samples. The experimental conditions were optimized. The method's specificity, relative accuracy, precision, and linearity were validated. Our data suggested that this method had good specificity, a relative bias of relative accuracy ranging from −0.8 to 1.4%, a correlation coefficient for the linear regression equation of 0.9953, a geometric coefficient of variation for intermediate precision ranges from 2.0 to 3.5%, and a linear range of 50 to 150%. This method significantly improves the quality control and release inspection efficiency of PTH1–34 and may be further developed and validated as an alternative to the existing United States Pharmacopeia and European Pharmacopoeia inclusion methods. This method also provides a platform for the high-throughput screening of PTH1–34 analogs.

In vitro comparative quality assessment of different brands of hydrochlorothiazide tablets marketed in Northeast Ethiopia

BackgroundThis study aimed to comparatively evaluate the quality and physicochemical bioequivalence of commercially available brands of hydrochlorothiazide (HCT) tablets in community pharmacies in Dessie town, Northeast Ethiopia.MethodsExperimental cross-sectional study design was applied using pharmacopeia and non-pharmacopeia methods. The difference (f1) and similarity (f2) factors were calculated to assess the in vitro bioequivalence of generic products with the comparator.ResultThe study results revealed that all investigated brands contained the required active pharmaceutical ingredients (APIs). The friability test results were concordant with the United States Pharmacopeia (USP) (&amp;lt;1%) for eight brands; however, brand NF3 (1.36%) failed to pass the specification limit. The hardness levels of the brands NF3 (24.20 ± 7.32 N), NF5 (32.19 ± 4.78 N), and NF9 (35.02 ± 3.12 N) were below the specification limit (39.23 N, USP 2019). The weight variation results of all generic products complied with the USP specification requirement. In the quantitative assay results, the minimum and maximum API contents were 97.4 ± 0.02 (NF6) and 105.8 ± 0.02 (NF8), respectively, which are within the limit specified by the USP (90%–110%). Similarly, all samples met the disintegration time limit (i.e., ≤30 min) and drug-releasing tolerance limit (API released more than 60% within 60 min) requirements. The f2 values were &amp;gt;50, and the f1 values were &amp;lt;15 for all sampled brands.ConclusionThe majority of the sampled brands of HCT tablets met the quality requirements as per USP official test specifications. From the similarity and difference factor values, all studied brands were shown to be equivalent.

Factorial design-aided derivatization-free fluorimetric ultrasensitive assay of vonoprazan with application in uniformity of dosage units and plasma samples analysis: Comprehensive and comparative greenness and whiteness assessment

This study presents a novel derivatization-free spectrofluorimetric method for the quantification of vonoprazan (VPZ) that is characterized by its high sensitivity, environmental friendliness, and cost-effectiveness. Notably, this method eliminates the requirement for pre-derivatization, extraction procedures, large amounts of organic solvents, and/or expensive instrumentation, which distinguishes it from previous approaches. The approach employed in this study relies on the formation of an association complex between VPZand the xanthene dye acid red 87 (AR87) under acidic conditions. The stability of the VPZ-AR87 complex was determined to be remarkably high, with a complex formation constant (Kf) value exceeding 2 x 106 M−1. The fluorimetric measurements rely on the quantitative and selective quenchingof the dye’s native fluorescence emission at 545 nm. The experimental parameters were optimized utilizing a quality-by-design 23 full factorial design. This strategy yielded a highly favorable linearity range of 10.0 to 400.0 ng/mL, with a correlation coefficient (r) of 0.9997. The presented methodology exhibited a high level of sensitivity, as evidenced by its ability to detect concentrations as low as 1.2 ng/mL. This sensitivity enabled its successful application for the estimation of VPZ in human plasma samples with high %recoveries (98.21–101.67) and low %RSD values (<1.52). Furthermore, content uniformity testing of low-dose VPZ tablets was performed according to United States Pharmacopeia guidelines. Greenness and whiteness metrics analysis showed a significant advantage of the proposed method over previously reported fluorimetric methods. Validation of the developed approach was carried out in accordance with ICHQ2 (R1) guidelines.

Optimizing carry-over in automated dissolution system dissoBOT for paracetamol and diclofenac sodium analysis

In this work, an automated dissolution system (dissoBOT) was used for dissolution testing for the first time. Carry-over (CO) of the dissoBOT was determined for paracetamol (PA) and diclofenac sodium (DS), which are active pharmaceutical ingredients (APIs). Initially, partial method validation of the UV-VIS spectrophotometry method for PA and DS determination was performed by defining the limit of detection (LOD), the limit of quantification (LOQ), linear concentration range, accuracy, and precision. The LODs and LOQs were less than 0.01 mg/L for both APIs. The determined linear concentration ranges were from 1.00 mg/L to 30.00 mg/L for PA and from 0.50 mg/L to 3.50 mg/L for DS (the square of the correlation coefficient was greater than 0.9990, and the quality coefficient was less than 1.00 % for both APIs). The accuracy of the method was evaluated by calculating the recovery (Re) of the solutions of standards with known concentrations. The method for both APIs was deemed to be accurate (the average Re for PA and DS were 99.81 % and 101.43 %, respectively). Precision was evaluated by calculating the relative standard deviation (RSD). The method for PA and DS was deemed to be precise, as the RSD value for PA was 0.13 %, and for DS was 0.38 %. The volume (V) of the washing medium in both cleaning cycles performed by the dissoBOT system, as well as the medium dispensing V, were established, where the medium dispensing V was in accordance with the United States Pharmacopeia requirements. The CO of the dissoBOT system, using tap water as the washing medium, was determined to be less than 1.00 % for both APIs. The CO values for one cleaning cycle of the sampling station with a V of 2 mL was in the range of 1.24–1.54 %, for V of 5 mL was in the range of 0.78–0.93 %, and for V of 10 mL was in the range of 0.27–0.36 %. In addition, the CO of the dissoBOT, when employing two cleaning cycles of the sampling station (each V of 10 mL) was reduced (CO <0.20 %). Finally, the dissoBOT was successfully employed for the dissolution PA and DS tables.

Development of a simple and rapid Formulation and evaluation of Metformin HCl extended-release tablets in comparison with Glucophage® XR

Metformin HCl is the first-line therapy for type 2 diabetes. It is available in both immediate-release and extended-release tablet forms, with the extended-release tablet being more beneficial. In this study, 34 formulations using five sustained-release agents, alone or in combination, were evaluated. The granular flowability, angle of repose, bulk Density, tapped Density, compressibility index, and Hausner ratio were assessed. Furthermore, the compressed tablets were tested for appearance, hardness, friability, and in-vitro drug release. Eleven formulations were evaluated for dissolution profiles according to the standards specified in the United States Pharmacopeia. After calculating the similarity factor (f1) and difference factor (f2), eight formulations were identified for further investigation. The combination of xanthan gum and hypromellose (HPMC K100) demonstrated superior results regarding the sustained-release agent amount and tablet appearance. This noteworthy finding led to continuing the study to explore further formulations with different amounts of xanthan gum and Hypromellose K100. As a result, formulation F34 was identified as the optimal choice because of its higher drug-to-polymer ratio. In conclusion, the final formulation is a rapid, cost-effective, and straightforward method due to the less time required for drying, the amount of sustained-release agents, and the number of components.

Quality of medicines for Cardio-Vascular Diseases (CVDs) in the Ethiopian border with Kenya: The case of enalapril maleate and furosemide tablet quality in Borena and Gedeo zones.

Hypertension (HTN), a cardiovascular disease (CV), is a major public health challenge. Therefore, the quality of drugs used to treat it has become a major concern. Enalapril and furosemide are among the drugs prescribed to manage hypertension. Hence, this study is aimed at evaluating the quality of different brands of enalapril and furosemide tablets available in the Gedeo and Borena zones, southern Ethiopia. Thirteen generic brands of enalapril maleate (5 mg) and furosemide (40 mg) tablets were evaluated for visual defects, in vitro dissolution test, weight variations, friability, hardness, and disintegration tests. The analysis of active pharmaceutical ingredient (API) content was performed by high performance liquid chromatography (HPLC). Out of 55 samples, 7 (12.73%) failed to comply with the criteria for visual inspection; otherwise, all samples passed the identification test. Except for one brand of each of enalapril maleate and furosemide, all passed the dissolution test. The assay value showed that all enalapril maleate samples were within the limits of United States Pharmacopoeia (USP), 2020. Additionally, except for two batches, all furosemide samples were within the USP and British Pharmacopoeia (BP), 2020 standards. Out of 55 samples, 8% (2/25) and 6.67% (2/30) of enalapril maleate and furosemide tablets failed the uniformity of dosage units test per the USP-2020, respectively. All samples passed the disintegration test, and selected furosemide samples passed the microbial limit tests. However, 36% (9/25) and 20% (6/30) of enalapril maleate and furosemide samples failed to pass hardness test. Generally, from the total samples, 50.91% (28/55) were substandard (did not meet the specifications failing any one or more parameters assessed). The studied drugs circulating in the market did not meet some of the needed quality specifications. This could have brought a risk of reduced efficacy due to the distribution of poor quality medicines in the area.

PHARMA'S NITROSAMINE CHALLENGE: A REVIEW OF A CALL FOR VIGILANCE

Nitrosamines are potential carcinogens (cancer-causing agents) that can form in medications under specific conditions. The British Pharmacopoeia (BP) and the United States Pharmacopeia (USP) both set strict guidelines to minimize their presence. Nitrosamines form when nitrites and amines react in acidic environments, potentially occurring in the stomach or during drug production. They are classified as probable human carcinogens, meaning long-term exposure at high levels may increase cancer risk. Fortunately, nitrosamine levels in most medications are very low and unlikely to pose significant health risks. Both BP and USP have implemented a new general chapter: Nitrosamine Impurities (BP: 5.20 and USP: &lt;1469&gt;).These chapters outline acceptable intake limits for six specific nitrosamines and a four-step risk assessment and control strategy. They also detail testing procedures and analytical methods for detecting and measuring nitrosamines in medications. There are similarities between BP and USP as both set comparable acceptable intake limits for the same six nitrosamines. Also, both employ a similar four-step risk management approach. Moreover, both provide information on testing procedures and analytical methods. Nevertheless, there are few differences between both references. There may be slight variations in the specifics of analytical procedures (e.g., detection limits, chromatographic conditions).Regulatory agencies are actively monitoring and controlling nitrosamine levels in medications, ensuring patient safety. Both BP and USP play crucial roles in setting stringent standards and ensuring their consistent implementation across the pharmaceutical industry. Peer Review History: Received 28 March 2024; Revised 2 May 2024; Accepted 25 June; Available online 15 July 2024 Academic Editor: Dr. Nuray Arı, Ankara University, Turkiye, ari@ankara.edu.tr Average Peer review marks at initial stage: 6.0/10 Average Peer review marks at publication stage: 7.0/10 Reviewers: Dr. Maya Shaaban Eissa Hussein, Egyptian Russian University, Egypt, maya-shaaban@hotmail.com Dr. Michael Otakhor Erhunmwunse, St. Philomena Catholic Hospital, Nigeria,dedoctor4life@yahoo.com

Analysis of the microbial contamination in available cosmetic products from Samaru Market, Zaria, Kaduna State, Nigeria

The purpose of this investigation was to assess the level of microbial contamination of cosmetic goods found in Samaru Market, Zaria, Kaduna State, Nigeria. Ten samples of two distinct cosmetics: face powder (labeled as FP) and kohl (labeled as K); were obtained from merchants at Samaru Market. The samples were cultivated on nutrient agar and mannitol salt for the purposes of viable cell count, isolation, and microscopic identification. To further characterize the isolates from the agar, gram staining technique and biochemical tests (catalase, urease, indole, Voges-Proskauer, citrate utilization, and methyl red test) were employed. With the exception of samples K1 and FP2, every sample had total viable bacteria. The United States Pharmacopeia (USP) and Food and Drug Administration (FDA) standards of less than 103 cfu/ml of bacteria load for non-eye areas were exceeded by all samples except K2 and FP1. Sample FP5 had the highest count of 3.6 x 104cfu/ml, while sample K2 had the lowest count of 1.2 x102 cfu/ml. Microscopy, revealed the isolates on mannitol salt agar as rounded, elevated, flat, small, yellowish and pinkish with short rods. The nutrient agar colonies appeared to be short rod-like, mucoid, uneven, rough, and whitish in color. The biochemical characterization of the isolates was positive for catalase, citrate, Voges Proskauer, and motility test. In conclusion, some of the face powder and kohl samples in the study are dangerous to use since Bacillus spp. were isolated with a bacterial count that was greater than the acceptable limit.

Understand the Stabilization Engineering of Ascorbic Acid, Mapping the Scheme for Stabilization, and Advancement.

Vitamin C is extensively used in cosmetic formulation, howbeit stability is the supreme demerit that limits its use in beautifying products. Numerous techniques are being employed to inhibit the degradation of vitamin C caused by formulation components to facilitate the use in skin rejuvenating products. Diverse materials are being exercised in formulation to stabilize the ascorbic acid and ingredients selected in this formulation composition help for stabilization. The initial stable prototype is developed and further optimization is accomplished by applying the design of experiment tools. The stable pharmaceutical formulations were evaluated for the evaluation parameters and designated as two optimized formulations. The analytical method for the assay of ascorbic acid from the United States pharmacopeia and the related substance method from European pharmacopeia has been modified to be used for cream formulation. The DoE design exhibited that the stability of formulation is impacted by citric acid and tartaric acid but not by propylene glycol and glycerin. The analysis results of topical formulations for the evaluation parameter exhibited satisfactory results. The in-vitro release study method has been developed, optimized, and validated to fit the analysis. The in-vitro studies have been performed for selected compositions and both the formulation has similar kinds of release patterns. The stability study as per ICH guidelines exhibited that the product is stable for accelerated, intermediate, and room-temperature storage conditions. The optimized formulation shows constant release and permeation of ascorbic acid through the skin. The formulation with the combinations of citric acid, tartaric acid, and tocopherol is more stable and the degradation of vitamin C has been reduced significantly. The beaucoup strategies in the unique composition help to protect the degradation by inhibiting the multitudinous degradation pathways.

Analysis of the distribution and persistence of organophosphorus pesticides malathion and diazinon in herbal plants

Introduction. Determination of pesticide residues presence in herbal plants and preparations based on them is an important step in confirming safety at the stage of the quality control of herbal plants. The usage of organophosphate pesticides (OPs) for the purposes of treatment of medicinal plants in the growing process is increasing. Scientific sources provide information on the detection of OPs in herbal plants, including quantities exceeding the allowed percentage limits as it is settled in regulatory documentation. At the same time, the problem of the distribution of particular kinds of OPs in the organs of herbal plants and their persistence remains understudied.Aim. The present research aims to study the distribution in various parts of the herbal plants (marigolds, valerian, and stinging nettle) and the persistence of malathion and diazinon.Materials and methods. Stinging nettle, that grows everywhere, exclusively cultivated marigolds, and valerian were selected as model plants. All of the plants were divided into three equal groups. Young plant shoots were processed twice with "Aliot" products containing 570 g/l of malathion and "Terradox" containing 40 g/kg of diazinon. The first group of plants was processed with pesticides following the manufacturer's instructions. The second group was treated in quantities, that were three times higher than the recommended dosage. The third group (control), was not processed with pesticides. Samples of various parts of growing herbal plants were analyzed at certain time points with the HPLC-MS/MS method according to the developed methodology. In order to study the persistence, we carried out a repeated analysis of dried samples stored without access to sunlight 0.5 years after the first one according to the requirements of the State Pharmacopoeia of the Russian Federation XV.Results and discussion. The authors found malathion and diazinon in all of the analyzed parts of medicinal marigolds, in leaves and roots of nettle dioecious, in deciduous shoots and rhizomes with roots of valerian officinalis. The highest proportion of pesticides was discovered in underground plant organs. When processed according to the instructions, in marigold and nettle roots and in rhizomes with valerian roots 16.7 mg/kg, 4.5 mg/kg, and 1.7 mg/kg of malathion and 19.6 mg/kg, 4.1 mg/kg, and 1.5 mg/kg of diazinon were found, respectively. These quantities exceed the allowed limits. The quantity of pesticides in the flowers of medicinal marigolds does not exceed the permissible values. The research on the persistence of these OPs data demonstrates that malathion and diazinon persist in plant tissues for a long time.Conclusion. As a result of the research quantitative characteristics of the distribution of malathion and diazinon in various parts of medicinal marigolds, medicinal valerian, and dioecious nettle, as well as the rate and the extent of degradation of OPs during six months, were determined.

Method development and validation of Metformin HCL and Dapagliflozin by using RP-HPLC

AbstractThe prevalence of diabetes is increasing day by day as per a report by the year 2045, 1 out of every 8th individuals may suffer from diabetes. This research article focuses on developing and validating Metformin and Dapagliflozin in combination by using high-pressure liquid Chromatography (RP-HPLC). The validation of the method was followed as per the guidelines provided by the International Conference on Harmonization (ICH) and United States Pharmacopeia (USP). Separation of both drugs takes place in less than 4 min. This separation takes place using Phosphate buffer (pH 6.8) and acetonitrile in a 45:55 (v/v) ratio at a 1.0 mL min−1 flow rate. Furthermore, studies on both drugs were conducted by using the bulk and pharmaceutical dosage forms (Tablets). The developed method was accurate as drug recoveries in both cases of Metformin, and Dapagliflozin ranged between (100.8, 99.6, 98.8%) to (100.8, 99.3, and 101.5%) respectively having a concentration range of solutions between 70, 100 and 130 μg mL−1 dilution. The recommended method for simultaneous quantification of Metformin and Dapagliflozin was established and validated and no excipient interactions were found.

Elemental Impurities in Gelatine Capsules: Human Health Risk Assessment

INTRODUCTION. This work continues the authors’ earlier study on gelatine capsule contamination with elemental impurities, which resulted in proposing a list of elements for standardisation. To ensure the safe use of medicinal products in this dosage form, it is necessary to develop criteria for the quantitative assessment of potential human health risks associated with elemental impurities in gelatine capsule shells.AIM. This study aimed to determine the permitted daily concentration (PDC) limits for elemental impurities in gelatine capsules from a risk-based pharmaceutical quality control perspective.MATERIALS AND METHODS. The authors analysed their previous experimental data, the relevant Russian State Standard (GOST), the requirements of the State Pharmacopoeia of the Russian Federation and leading world pharmacopoeias (USA, UK, EU, China, Japan, and India), and the scientific literature published from 1980 to 2023 on the content of elemental impurities (Al, As, Cd, Cu, Cr, Cr, Fe, Hg, Mn, Pb, and Zn) in gelatine capsule shells and medical gelatine.RESULTS. When standardising the content of elemental impurities in gelatine capsule shells, it is necessary to consider not only the toxicity of impurities but also their potential to compromise the quality of gelatine. Complexing elements (Cd, Cu, Hg, Cr, and Zn) can affect the quality of gelatine at subtoxic concentrations. For Cd, Cu, and Hg, the authors recommended using the PDC limits specified in GOST 23058-89 Gelatine. Raw materials for the medical industry. Specifications. For Cr and Zn, the authors recommended adhering to the PDC limits specified in the State Pharmacopoeia of the Russian Federation, edition XIV, Monograph 2.1.0099.18 Gelatine. Lead affects the quality of gelatine at concentrations above the toxicity threshold, and arsenic does not cause clustering of gelatine molecules. For Pb and As, the authors recommended using the PDC limits specified in the State Pharmacopoeia of the Russian Federation, edition XV, General Monograph 1.1.0040 Elemental impurities. The authors proposed a conversion factor to account for the complexing potential of Al when limiting its content in gelatine capsule shells. The authors recommended assessing the risks to human health associated with Mn intake with gelatine capsule shells indirectly by listing total heavy metals as a quality attribute to be controlled at the level of medical gelatine. The content of Fe should also be standardised at the raw material level.CONCLUSIONS. The content of elemental impurities in gelatine capsule shells should not exceed the following limits: 45 µg/g for Al, 1.5 µg/g for As, 0.03 µg/g for Cd, 10 µg/g for Cr, 15 µg/g for Cu, 0.05 µg/g for Hg, 0.5 µg/g for Pb, and 30 µg/g for Zn. The standardisation of these elements in gelatine capsule shells will prevent negative effects on the human body and shell quality.