United States Pharmacopeia Research Articles

Solvent-Based and Matrix-Matched Calibration Methods on Analysis of Ceftiofur Residues in Milk and Pharmaceutical Samples Using a Novel HPLC Method.

The matrix effect is accepted as one of the critical factors that affect trueness, and it is especially important in the analysis of critical compounds, such as drugs, toxins and pesticides, in complex matrices. Ceftiofur (CEF) is a leading drug used in dairy industry for pulmonary infections. Because milk has a complex matrix, which is rich in fats, proteins and many other compounds, the determination of CEF in milk products deals with issues of trueness. On the other hand, pharmaceuticals also have a complex composition as they contain not only the active pharmaceutical ingredient but also many excipients, such as preservatives and pH modifiers. Due to its frequent use, its residues can be found in meat products or exist as an excreted compound in urine, milk and so on. The aim of this study was to investigate the effect of different calibration methods on quantitative estimation of CEF in milk and pharmaceutical samples. CEF was analysed using a new HPLC method, in which separation was achieved on a C18 bonded fused-core silica particle column by using isocratic elution; the method was optimized by testing different chromatographic conditions and validated according to the ICH Q2(R1) and United States Pharmacopeia guidelines. Interestingly, it was found that CEF signals in milk samples were higher than the ones at the same level prepared in calibration solutions with a ratio of 11.28:1. This finding reveals the necessity of matrix-matched calibration for accurate quantitative determination of CEF in milk samples. Moreover, the milk in the market and the most used pharmaceutical formulations were analysed using the current method.

Determination and Quantification of Related Impurity Substances in Elvitegravir Drug Substance by Full Factorial Design Evaluated Liquid Chromatography Method

ABSTRACTHerein, our work deals with developing a rapid, accurate, and reliable high‐performance liquid chromatographic technique with the application of quality by design (QbD) experimental tool to quantify Elvitegravir drug (Integrase inhibitors of antiretroviral drug) and its novel related impurities at low levels. Further, this unique method has been validated to prove its consistency. Separation of N‐methyl Elvitegravir (Impurity‐I), 2‐fluoro Elvitegravir (Impurity‐II), and Elvitegravir isopropyl ester (Impurity‐III) in Elvitegravir drug substance was executed by using Kinetex C18 column (150 mm × 2.1 mm × 1.7 µm) with water, acetonitrile, formic acid, and triethylamine (690:300:6:2, v/v/v/v/), mobile phase (MB‐A) and acetonitrile, formic acid and triethylamine (990:6:2, v/v/v), MB‐B. This developed analytical technique gave a well‐separated peak at the retention times of 9.126 min (Elvitegravir), 7.713 min (Impurity‐I), 7.972 min (Impurity‐II), and 8.548 min (Impurity‐III) adequate with the peak properties as per the United States Pharmacopeia guideline. The method's sensitivity and linearity are established by its detection and quantification limits at low levels with a correlation coefficient of 0.998. The method's repeatability, specificity, and accuracy suggest that this developed technique is a reliable determination strategy for Elvitegravir drug substance and its related impurities (Impurity‐I, Impurity‐II, and Impurity‐III) in a simple, feasible, and affordable way.

Assessment of miligram(Mg) content of some notable analgesics used by residents of Maiduguri Metropolis: evidence from high performance liquid chromatographic technique

Diclofenac sodium and paracetamol are Over the counter (OTC) medications used as analgesic and antipyretic agents to relieve pains, fever and headaches. The aim of this work was determine the mg content of paracetamol and diclofenac sodium in selected samples across the Maiduguri metropolis using High Performance liquid chromatography (HPLC) method. For paracetamol samples an intersil ODS-3V column (150 mm × 4.6 mm; 5 μm pore size) was used at the temperature of 35oC the mobile phase was methanol: water (20:80) using isocratic elution at the flow rate of 2 mL/min, injection volume of 10 μL and a diode array detector. For diclofenac sodium samples, the chromatographic conditions were the same except the mobile phase which was methanol: water (63:37), flow rate of 0.8 mL min, injection volume of 20 μL and column temperature was set at 30 oC. A total of 45 samples were analysed; which comprised of paracetamol tablet, paracetamol syrup and diclofenac sodium tablet which were randomly selected from three different sources; hospital pharmacy, community pharmacy and drug patent stores. The percentage mg content for paracetamol tablets ranged from 48 to 83 % while that of the paracetamol syrups ranged from 72 to 120 % and finally diclofenac sodium tablets ranged from 73 to 174 %. Adopting the United State Pharmacopoeia (USP) as reference for assessment tool, it was observed that all the paracetamol tablet samples failed, 4 out of 15 paracetamol syrup samples failed, and 11 out of 15 diclofenac sodium tablet samples failed. There was statistical significance (p< 0.05) between class of drug and percentage mg content but there was no significance (p< 0.05) between source of drug and percentage constituent. HPLC technique was used successfully for quantitative determination of paracetamol and diclofenac sodium dosage forms.

A reduced graphene oxide-coated conductive surgical silk suture targeting microresistance sensing changes for wound healing

Conventional sutures used in surgical procedures often lack the capability to effectively monitor physical and chemical activities or the microbial environment of surgical wounds due to their inadequate mechanical properties, insufficient electrical accuracy and unstability. Here, we present a straightforward layer-by-layer coating technique that utilizes 3-glycidoxypropyltrimethoxysilane (CA), graphene oxide (GO), and ascorbic acid (AA) to develop conductive silk-based surgical sutures (CA-rGSFS). The CA-rGSFS feature a continuous reduced graphene oxide (rGO) film on their surface, forming robust hydrogen bonds with silk fibroin. The reduction process of rGO is confirmed through Raman analysis, demonstrating an enhanced D peak to G peak ratio. Notably, the CA-rGSFS exhibit exceptional mechanical properties and efficient electron transmission, with a knot-pull tensile strength of 2089.72 ± 1.20 cN and an electrical conductivity of 130.30 ± 11.34 S/m, respectively, meeting the requirements specified by the United States Pharmacopeia (USP) for 2-0 sutures. These novel CA-rGSFS demonstrate the ability to accurately track resistance changes in various fluid environments with rapid response, including saline, intestinal, and gastric fluids. The suture also retains remarkable stretchablility and stability even after enduring 3000 tensile cycles, highlighting their potential for precise surgical site monitoring during the wound healing process.

In Vitro Analysis of Aerodynamic Properties and Co-Deposition of a Fixed-Dose Combination of Fluticasone Furoate, Umeclidinium Bromide, and Vilanterol Trifenatate.

Effective airway delivery of a fixed-dose combination of triple-aerosolized inhaled corticosteroid (ICS)/long-acting beta agonist (LABA)/long-acting muscarinic antagonist (LAMA) is likely to positively affect therapeutic responses predicted in patients with asthma and chronic obstructive pulmonary disease. This study aimed to conduct in vitro fluticasone furoate, vilanterol trifenatate, and umeclidinium bromide depositions in a Next Generation Impactor. The aerodynamic properties of these inhaled medications influence the spatial distribution and drug abundance, particularly in the smaller airways, to reverse or alleviate disease pathology. The Next Generation Impactor was used to demonstrate the aerodynamic particle size distributions of fluticasone furoate, vilanterol trifenatate, and umeclidinium bromide delivered from a dry powder inhaler at different flow rates across all stages of the impactors. This in vitro study analyzed the distribution pattern of individual drug components to simulate mono-component deposition and co-deposition in the official model in the United States Pharmacopeia. An Andersen cascade impactor together with scanning electron microscope-energy-dispersive X-ray was employed to observe the drug deposition on each stage of the impactor. We found that the distribution pattern of each component at the same cascade level was comparable, and the aerosol particles of the three drugs reached the in vitro representation of the lower airway compartment. The specified flow rates generated the desired fine particle fraction, fine particle dose, and mass median aerodynamic diameter. Our results also demonstrated visualized deposition patterns of the delivered drugs from different stages of the cascade impactor that may predict deposition as it occurs in vivo. Spatial distribution and abundance of ICS/LABA/LAMA in the same cascade levels were closely comparable, and the aerosol particles were able to reach the small aerosol-sized cascades at the lower levels to some extent.

Post-marketing quality evaluation of oxytocin injection and assessment of associated factors among selected health facilities in Addis Ababa, Ethiopia

Oxytocin is the principal drug and the primary choice for labor induction and postpartum hemorrhage prevention and treatment. The problems associated with oxytocin are not usually from its effectiveness, but they are from its compromised quality which may occur at the point of manufacturing, transportation, and storage. The main objective of this study was to assess the status of oxytocin injection quality and associated factors in the health facilities located in Addis Ababa city, Ethiopia. A laboratory based instrumental quality testing alongside a cross sectional study design was used to evaluate oxytocin injection quality in Addis Ababa city administration from January to June, 2022 according to United States Pharmacopeia (USP 20), and the World Health Organization guideline of post-market medicine quality assessment. Binary logistic regression and cross tabulation analysis were conducted using SPSS 26. Significance was considered at p ≤ 0.05. Out of 107 tested oxytocin injection samples, 92.5% met the limit for oxytocin content, 81.3% for sterility test, and 91.6% for pH value. Overall, quality failure rate was 23.4%, while sterility test failure rate was 18.7%. Lack of reliable refrigerated storage condition [(AOR = 5.62, 95% CI: (1.87, 16.88)], lack of effective cold chain system during distribution [(AOR = 5.5, 95% CI: (1.53, 19.74)], and weak national medicine regulatory system [(AOR = 3.23, 95% CI: (1.13, 9.23)] were among the significantly associated factors for the failure of some of the brands. The study demonstrated that oxytocin injection quality failure rate, failing to meet at least one quality test requirement, is demonstrated in the health facilities of Addis Ababa. The determinant factors for the reported failures are related to storage, distribution, and regulatory system. Hence, these should be addressed by strictly adhering in to the national regulation and providing a comprehensive health promotion on rational use of oxytocin injection should be implemented to assure its quality and safety.

Evaluation of Risk Factors Associated with Selected Elements in Veterinary Active Pharmaceutical Ingredients Using ICP-MS.

One of the major concerns for animal health is the pollution of food and medicines given to animals by non-essential and toxic elements, which also poses a risk to human health via the food chain. The essential (Ca, Cr, Mn, Fe, Co, and Ni) and non-essential elements (Li, Ti, V, Ga, Ag, Cd, In, Ba, Bi, Th, and U) were monitored using inductively coupled plasma mass spectrometry (ICP-MS) in veterinary active pharmaceutical ingredients (V APIs). Samples were divided into four groups including antibiotic (14 samples), anthelmintic (7 samples), anticoccidial (5 samples), and externally used (5 samples). The results of the antibiotic group had the highest concentrations of most elements. The concentrations of the targeted elements were below the permissible limits as recommended by the United States Pharmacopeia (USP). The target hazard quotient (THQ) and the total target hazard quotient (TTHQ) were applied to evaluate the animal health risk associated with the exposure of the target elements in V API samples; the results showed that elements do not pose any risk to animals in all samples as indicated by THQ values less than 1. Validation parameters performed in this study showed good accuracy and validity of the ICP-MS analysis method, with good linearity (R2 ˃ 0.990), and the relative standard deviations (%RSD) were < 4% for all target elements. Analysis of variance (ANOVA-one way) was used to compare the means of veterinary drug groups for all targeted elements. The results showed that all elements have p-values < 0.05 except 52Cr and 54Fe.

Relationship between Prices and Quality of Essential Medicines from Different Manufacturers Collected in Cameroon, the Democratic Republic of the Congo, and Nigeria.

Achieving universal access to affordable medicines and at the same time ensuring the quality of medicines presents a challenge, especially in low- and middle-income countries. Here, the relationship between medicine prices and medicine quality was investigated in three African countries. From different types of health facilities and medicine vendors, 711 samples of 18 different essential medicines were purchased and analyzed for quality (assay and dissolution) according to the United States Pharmacopeia. Without exception, all originator brand medicines and all SRA generics (generic medicines manufactured in countries with stringent regulatory authorities [SRAs]) complied with pharmacopeial specifications. In contrast, 21.1% of the non-SRA generics (manufactured in countries without SRAs) were substandard. The median prices of originator brands and SRA generics were three times and two times higher than those of non-SRA generics, respectively. Within the non-SRA generics, no positive correlation was observed between medicine quality and medicine price. Medicines manufactured in India, China, or African countries showed similar quality and similar prices. Only a single WHO-prequalified medicine sample was found among the 711 samples. Non-SRA generic medicines produced by manufacturers for which WHO had published Public Inspection Reports showed a significantly lower rate of substandard medicines (7.3%) and, at the same time, significantly lower prices (by 33%) than other non-SRA generics. Falsified medicines (total 2.0%) were found among all categories of medicines and had prices similar to those of non-SRA generics. Our findings indicate that adequate quality assurance does not necessarily imply an increase in medicine prices.

Development and Validation of FTIR Spectroscopic Method for the Quantitative Estimation of Lornoxicam in Tablet Dosage Form.

Lornoxicam is available in the market as a solid dosage form, particularly tablets. Liquid chromatography has been the recommended assay procedure for lornoxicam in various pharmacopeias. While going through the literature, it was observed that for the analysis of lornoxicam, no FTIR based method was found. The present study involves the development of a novel, rapid, superior, labor-free, non-destructive, and economic FTIR-based analytical technique for the analysis of lornoxicam in both bulk and tablet formulations. International Council validated the method for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines Q2A and Q2B in accordance with the United States Food and Drug Administration (USFDA) guidance and by United States Pharmacopoeia (USP). FTIR based method is extremely precise, quite linear, very accurate, and has adequate ruggedness. The developed method can be of potential use in the routine quantitative drug analysis of lornoxicam in the pharmaceutical industry for quality control purposes.

Development and Validation of an ICP‐OES Method to Determine Extractable and Leachable Metals in HDPE (Plastic) Pharmaceutical Packaging Material

ABSTRACTThe safety and effectiveness of pharmaceutical medicines depend heavily on extractables and leachables. Patients may be adversely affected by contaminants that enter drug products through packing materials. As a result, regulatory organizations like the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) have set standards and regulations for evaluating and managing extractables and leachables. Characterizing the packing materials, carrying out extraction experiments and checking the extracted solutions for contaminants are all parts of this research. As part of the process for approving new drugs, regulatory agencies make use of these data. In present work, an inductively coupled plasma optical emission spectroscopy (ICP‐OES) method is developed and validated for quantifying trace elements from a high‐density polyethylene (HDPE) packaging material. The approach delineated in accordance with United States Pharmacopoeia (USP) &lt;661.1&gt; and &lt;661.2&gt; for the comprehensive analysis of 16 metallic elements including aluminium, arsenic, cadmium, chromium, cobalt, lead, mercury, nickel, titanium, vanadium, zinc, zirconium, barium, manganese, calcium and tin is applicable for evaluating the efficacy of packaging materials. The method detection limits (MDLs) complied as per USP 39‐NF 34 &lt;661.1&gt; along with relative standard deviations (RSDs) obtained were ranging from 0.3% to 3.1% and recoveries of all elements spiked at two different trace levels in HDPE samples were within 97%–110%, providing sensitive, accurate and reproducible methodology.

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.

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.