Stability indicating high performance thin layer chromatography method development and validation for quantitative determination of tetracycline hydrochloride in tetracycline hydrochloride active pharmaceutical ingredient (API) and its dosage forms.

Simple, quick, cost-effective, and environmentally friendly analytical methods for quality assurance and control roles for different medicines, including Tetrcyclines, are most significantly needed. Also, different thin layer chromatography (TLC)-based methods for tetracycline identification exist, but high performance thin layer chromatography methods based on modern state- of- the art equipment are still nonexistent. Thus, in this study, analytical method development and verification were done by high performance thin layer chromatography (HPTLC) (using an automated equipment model) using glass plates coated with silica gel 60 F254 after treating with 10% Na2EDTA. Validation was carried out according to International Council for Harmonization (ICH) guidelines. A mobile phase formed from ethyl acetate, acetonitrile, methanol, and 1% aqueous ammonia in the composition of 4.4:19.6:10:6 volume to volume ratio (V/V) was used. Rf value, percentage recoveries, linearity ranges, limit of detection (LOD), and limit of quantitation (LOQ) for the developed HPTLC method were 0.28, 100.83-106.25%, 160-560 ng/band (r2 values of 0.9999), 31.9 ng/band, and 96.7 ng/band, respectively. The results of the sample assays conducted using the new method and the United States Pharmacopoeia (USP) high performance liquid chromatography (HPLC) method were 91.59% to 108.3% and 90.83% to 102.85%, respectively. The F test for the aforementioned methods was 2.01, which is smaller than the tabulated F value of 5.05 with 5 degrees of freedom at a 95% confidence range, proving that the newly developed HPTLC and HPLC pharmacopoeial methods can be used interchangeably.The newly developed HPTLC method is easy, economical, specific, accurate, and roboust, thus it can be employed in a range of settings that require quality control and assurance activities of tetracycline hydrochloride (TC-HCl) in bulk and ointment dosage forms.

Quality Assessment of Selected Essential Antimicrobial Drugs from Drug Retail Outlets of Selected Cities in Eastern Ethiopia.

The prevalence of substandard and falsified (SF) antimicrobial drugs is increasing around the globe. This poses a great concern for the healthcare system. The consumption of SF antimicrobial drugs has the potential to result in treatment failure, emergence and development of antimicrobial resistance, and ultimately a rise in mortality rate. The objective of this study was to assess the quality of four commonly used antimicrobials marketed in the cities of Dire Dawa and Jijiga and the town of Togo-Wuchale, which have high potential for illegal drug trade activities in Ethiopia because they are located near the border with Somalia. A total of 54 brands/samples of amoxicillin, amoxicillin/clavulanic acid, ciprofloxacin, and norfloxacin formulations were collected covertly from 43 facilities using a convenience sampling strategy from March 16 to March 29, 2022. The samples were first screened using Global Pharma Health Fund (GPHF)-Minilab protocols and then analyzed using U.S. Pharmacopoeial and British Pharmacopoeia official methods. The quality evaluation detected no falsified product; however, it showed that 14.3% of the samples failed the GPHF-Minilab screening test semiquantitatively. Overall, 22.2% of the products analyzed did not meet any of pharmacopoeial specifications assessed: 13%, 12.2%, and 11.1% of the products failed in assay, dissolution, and weight variation, respectively. Additionally, 56.3% of amoxicillin samples, 60% of amoxicillin/clavulanate, 20% of ciprofloxacin, and 54.5% of norfloxacin samples were found to be pharmaceutically nonequivalent with their respective comparator products regarding dissolution profiles. The study showed the presence of substandard antimicrobial medicines in the eastern Ethiopian market.

Development and validation of a high-performance thin layer chromatography method for the simultaneous determination of amoxicillin and clavulanic acid combinations in tablet dosage forms.

A simple and sensitive high-performance thin layer chromatography (HPTLC) method was developed and validated as per the International Council for Harmonization (ICH) guidelines for the simultaneous determination of amoxicillin (AMX) and clavulanic acid (CLA) combinations in tablet formulations. Chromatography was performed on precoated glass plates with normal phase silica gel 60 F254. The mobile phase was acetone:ethyl acetate:glacial acetic acid:water (11:9:4:2 (v/v)). The plate was scanned at a wavelength of 428 nm after derivatization with ninhydrin. The validation of the method revealed that the linearity range lies between 400 and 1200 ng/band for AMX and 100-300 ng/band for CLA, with coefficients of determination of 0.9997 and 0.9966, respectively. Recoveries in standard addition accuracy studies were 100.3 % for AMX and 96.75 % for CLA. The limit of detection (LOD) and limit of quantitation (LOQ) of the developed method are 20.3 ng/band and 61.6 ng/band for AMX and 18.5 ng/band and 56.2 ng/band for CLA, respectively. The new, novel high-performance thin layer chromatography (HPTLC) method that was successfully developed in this study was applied for the simultaneous determination of AMX and CLA in their fixed-dose tablet dosage forms obtained from retail pharmacies and offered comparable results with the official British Pharmacopoeial high-performance liquid chromatography (HPLC) method.

Quality of veterinary anthelmintic drugs marketed in Gondar Zones, North West Ethiopia; presence of poor-quality medicines.

The presence of poor-quality veterinary drugs hampers the effectiveness of animal health care systems. It may produce danger to human safety through animal-derived food products that are consumed by the people. Thus, this study assessed the quality of veterinary albendazole, fenbendazole and ivermectin boluses/tablets marketed in Gondar Zones, North West Ethiopia. A total of 42 samples were collected from all government veterinary clinics and private veterinary pharmacies in Gondar zones by mystery shoppers from October, 2020 to January, 2021. All samples were visually and physically inspected for proper labeling and packaging. Samples were evaluated based on Pharmacopoeias and manufacturers' methods for identification, assay, dosage uniformity, dissolution, disintegration, hardness, and friability tests. All samples passed the visual inspection criteria outlined in the joint WHO/FIP/USP checklist. In general, 80.95% (34/42) of the products examined were substandard failing one or more quality test parameters, including all albendazole (30/30) and fenbendazole (4/4) samples. However, all of the ivermectin samples (8/8) passed the quality test parameters investigated in this work. The study had indicated that low quality veterinary albendazole and fenbendazole products are incredibly common in the study sites. The most crucial quality features investigated as failure were friability and disintegration. Thus, regulations and enforcements that guarantee quality of veterinary anthelminthic medications should be strictly in place in the study area and in the country.

Assessment of the Regulatory Approval Process of Medical Devices in Ethiopia: A Mixed Sequential Explanatory Study.

BACKGROUND: Cognizant of indispensable role as important health intervention tools, the global medical devices industry continues to bring new medical devices with varying degrees of technologies and complexities. Ensuring the safety, good performance and timely access of them have become challenging for regulatory authorities, particularly for developing countries including Ethiopia. In Ethiopia, the role of the regulatory authority is complicated further because of the lack of specific policies. Medical devices regulation is still being dealt under drug policy. OBJECTIVES: This study was aimed to assess the regulatory approval processes of medical devices in Ethiopia. METHODS: A mixed sequential explanatory study design was employed. Quantitative data were collected using a structured self-administered questionnaire and standard checklist; qualitative data were collected through in-depth interviews using a semi-structured guide. RESULTS: Retrospective trend analysis (2015 to 2018) indicated that 3,804 medical devices were registered in Ethiopia. Findings from the quantitative study indicated that 73.3% of regulatory experts had commendable knowledge on the medical devices regulatory system. However, gaps were identified in inspection and auditing (63.8%), practically understanding the system and procedures (24.3%), and having competencies in executing the critical core functions (6.9%). The top five challenges reported include (i) lack of capacity to assess dossiers (80.8%); (ii) lack of effective legislation (64.1%); (iii) provision of ambiguous feedback on deficiencies after dossier evaluations and delay in their communication (63.9%); (iv) long waiting time for approval (61.1%); and (v) lack of experienced and qualified staff (55.7%). In addition, the absence of a specific policy for medical device regulation presents a great hurdle. CONCLUSION: Basic functional systems and procedures for the regulation of medical devices in Ethiopia are present. However, there are still gaps that are impeding effective regulation of medical devices especially for those with advanced features and complex-monitoring modalities.

Determination of the level of heavy metals and assessment of their safety in cow's milk collected from Butajira and Meskan districts, south central Ethiopia.

Milk is a complete food useful to promote growth and development of the infant mammals as it contains vital nutrients (proteins, essential fats, vitamins, and minerals) in a balanced proportion. It is also a nutritious food for adults too. Milk can also contain hazardous chemicals and contaminants including heavy metals which can be a risk for health. This study was aimed at determining the level of heavy metals in cow's milk collected from Butajira and Meskan districts, south Ethiopia. Cows' milk was collected from 193 healthy lactating cows. Samples were digested by optimized microwave digestion method using HNO3 and H2O2. Analysis was done using ICP-OES for Cd, Cr, Cu, Fe, Mn, Ni, Pb, and Zn levels. MP-AES was used for Ca, Mg, K, and Na. Ni was not detected in all samples. Concentrations of heavy metals in the studied samples were Cd (0.0-0.03), Cr (0.0-0.4), Cu (0.03-1.1), Fe (0.0-1.9), Mn (0.0-0.7), Pb (0.0-12.3), Zn (0.0-8.2), Ca (380.1-532.4), Mg (159.6-397.9), K (1114.2-1685.8), and Na (495.9-1298.3) ppm. These values were compared with permissible values prescribed by different international organizations and available literatures. Cd, Cr, Cu, Mn, Pb, Zn, and Mg levels were found above the permissible limits. Thus, special attention needs to be given to the level of heavy metals in cows' milk, as they are difficult to remove from the body. Their accumulation to a level greater than their permissible limit could be deleterious to the health of the user.

Iodine status, household salt iodine content, knowledge and practice assessment among pregnant women in Butajira, South Central Ethiopia.

BACKGROUND: Iodine is one of the crucial micronutrients needed by the human body, and is vitally important during pregnancy. This study aimed to determine the relationship between the iodine status of pregnant women and their knowledge, and practices regarding iodized salt. All participants were enrolled in the Butajira nutrition, mental health and pregnancy (BUNMAP) cohort, Butajira, Ethiopia in February-May, 2019. METHODS: In this cross-sectional study, 152 pregnant women without hypertension or known thyroid disease before or during pregnancy were randomly selected from the BUNMAP mother to child cohort (n = 832). Spot urine samples were collected to estimate the level of urinary iodine concentration (UIC). Salt samples were also collected from their homes. The Sandall-Kolthoff (S-K) method was used to measure the level of iodine in the urine samples, and iodometric titration was used to measure the level of iodine in the salt. Data was entered and cleaned using Epi-info version 3.5.3 and then exported to SPSS version 20 for further analysis. Multivariate logistic regression analysis was performed to identify associations in the collected data. RESULTS: The WHO recommended level of iodine for populations of pregnant women is 150-249 F06Dg/L. The median UIC among pregnant women in this study was 151.2 µg/L [interquartile range (IQR) = 85.5-236.2 F06Dg/L], at the low end of this range. About half (49.65%) of the participants were likely to be iodine deficient. There was a significant association between having a formal job (AOR = 2.56; CI = 1.11-5.96) and iodine sufficiency. Based on a cutoff of >15 ppm (mg/kg), 91.7% (95% CI: 87.2-96.2) of the salts collected from the household had adequate iodine content. The median iodine level of the collected salt samples was 34.9 mg/kg (ppm) (IQR = 24.2-44.6 mg/kg). CONCLUSIONS: The UNICEF 2018 guidelines for adequate iodine nutrition in pregnant women include both a recommended median range of 150-249 µg/L, and an upper limit of 20% on the fraction of the population with UIC below 50 µg/L. Because our study population's median level is 151.2 µg/L and the percentage of pregnant women with urinary iodine concentration of less than 50 µg/L is 9.7% (14/145), the women received adequate iodine nutrition. The availability of adequately iodized salt in households is more than 90%, as recommended by WHO. In light of previous iodine deficiency in this region of Ethiopia, the salt iodization program promotes the health of babies and mothers.

Securing the Chain of Custody and Integrity of Data in a Global North-South Partnership to Monitor the Quality of Essential Medicines.

Substandard and falsified (SF) pharmaceuticals account for an estimated 10% of the pharmaceutical supply chain in low- and middle-income countries (LMICs), where a lack of regulatory and laboratory resources limits the ability to conduct effective post-market surveillance and allows SF products to penetrate the supply chain. The Distributed Pharmaceutical Analysis Laboratory (DPAL) was established in 2014 to expand testing of pharmaceutical dosage forms sourced from LMICs; DPAL is an alliance of academic institutions throughout the United States and abroad that provides high-quality, validated chemical analysis of pharmaceutical dosage forms sourced from partners in LMICs. Results from analysis are reported to relevant regulatory agencies and are used to inform purchasing decisions made by in-country stakeholders. As the DPAL program has expanded to testing more than 1,000 pharmaceutical dosage forms annually, challenges have surfaced regarding data management and sample tracking. Here, we describe a pilot project between DPAL and ARTiFACTs that applies the blockchain to organize and manage key data generated during the DPAL workflow, including a sample's progress through the workflow, its physical location, provenance of metadata, and lab reputability. Recording time and date stamps with these data will create a permanent and verifiable chain of custody for samples. This secure, distributed ledger will be linked to an easy-to-use dashboard, allowing stakeholders to view results and experimental details for each sample in real time and verify the integrity of DPAL analysis data. Introducing this blockchain-based system as a pilot will allow us to test the technology with real users analyzing real samples. Feedback from users will be recorded and necessary adjustments will be made to the system before the implementation of blockchain across all DPAL sites. Anticipated benefits of implementing the blockchain technology for managing DPAL data include efficient management for routing work, increasing throughput, creating a chain of custody for samples and their data in alignment with the distributed nature of DPAL, and using the analysis results to detect patterns of quality within and across brands of products and develop enhanced sampling techniques and best practices.

Substandard Cisplatin Found While Screening the Quality of Anticancer Drugs From Addis Ababa, Ethiopia.

PURPOSE: A postmarket evaluation of chemotherapy dosage forms in Ethiopia was conducted to test the accuracy of the chemoPAD, a paper analytical device for drug quality screening. MATERIALS AND METHODS: In September of 2018 in Addis Ababa, Ethiopia, 41 anticancer drug dosage forms (representing 4 active ingredients, 5 brands, and 7 lot numbers) were collected and were rapidly screened for quality using a chemotherapy paper analytical device (chemoPAD). Confirmatory analysis via high performance liquid chromatography was conducted. RESULTS: The chemoPAD showed that the correct active pharmaceutical ingredient was present in doxorubicin, methotrexate, and oxaliplatin injectable dosage forms. However, 11 of 20 cisplatin samples failed the screening test. Confirmatory assay by high-performance liquid chromatography showed that all 20 cisplatin samples-comprising three lot numbers of a product stated to be Cisteen-were substandard, containing on average 54% ± 6% of the stated cisplatin content. Inductively coupled plasma optical emission spectroscopy analysis of five representative samples found 57% to 71% of the platinum that should have been present. The sensitivity of the chemoPAD for detection of falsified products could not be measured (as none were present in these samples), but the selectivity was 100% (no false positives). The sensitivity for detection of substandard products was 55%, and the selectivity was 100% (no false positives). CONCLUSION: Although instrumental analysis by pharmacopeia methods must remain the gold standard for assessing overall drug quality, these methods are time consuming and patients could be exposed to a bad-quality drug while clinical workers wait for testing to be performed. The chemoPAD technology could allow clinicians to check at the point of use for serious problems in the quality of chemotherapy drugs on a weekly or monthly schedule.

Paper Analytic Device to Detect the Presence of Four Chemotherapy Drugs.

A paper analytic device, the chemoPAD, was developed and validated to visually detect methotrexate, doxorubicin, cisplatin, and oxaliplatin at concentrations commonly found in injectable dosage forms. By testing residual solution after patient treatment, the chemoPAD can be used to monitor drug quality without restriction of patient access to medication. The chemoPAD is produced by wax printing on Ahlstrom paper to create separate reaction areas and deposits small amounts of chemicals to create color changes in response to different active pharmaceutical ingredients (APIs). This creates a unique color bar code to identify each medication. Internal validation studies show that the chemoPAD has excellent sensitivity and specificity to differentiate between samples of 100% and 0% API, which is the distinction relevant to the majority of reported falsified chemotherapy cases. The platinum-containing drugs, cisplatin and oxaliplatin, can be detected semiquantitatively. The cards can be read either visually by comparison with a standard image or by using computer image analysis. Dosage forms were collected from the Ethiopian health care system and analyzed with the chemoPAD followed by high-performance liquid chromatography. A substandard sample was discovered and reported to the Ethiopian Food Medicine and Healthcare Administration and Control Authority.

Assessment of the Use and Status of New Drug Information Centers in a Developing Country, Ethiopia: The Case of Public University Hospital Drug Information Centers.

INTRODUCTION: Drug information center (DIC), in most cases, is part and parcel of pharmacy service established as a unit that deals with offering recent, balanced, truthful facts about drugs to the public, patients, and health care professionals. OBJECTIVE: To assess the query receiving and response trends by the drug information centers (DICs) found in main university affiliated teaching health care institutes in Ethiopia. SETTINGS: The drug information centers located in Mekelle, Gondar, Jimma, Tikur Anbessa Specialized University Hospitals, and St. Peter Public Hospital, Ethiopia. METHODS: It employed analytical, descriptive (cross-sectional), and retrospective methods. The study was performed from June to August, 2015. All the available documented data were gathered with the help of checklist and questionnaire (self-administered). RESULTS: A total of 439 queries submitted to the DICs during their active service period were included in this study of which 407 were found to be suitable for this assessment. The highest inquiries had come from public hospitals (60 %) from health care workers (95.1 %), out of which pharmacists were the highest (63.57 %) submitters, followed by health care students (12.7 %). The major purposes of query submission were to improve treatment outcome of patients (33.9 %) and then to update the knowledge (25.1 %) although 39.3 % of the queries did not document it. The most common requests concern drug interaction (19.7 %) followed by therapeutic use (17.8 %) and the major pharmacological group is about antimicrobials (23.3 %) followed by antihypertensives (11.4 %). Web sites (31.4 %) were the most highly used references followed by Micromedex (19.0 %). CONCLUSION: The assessment of the DICs had shown that it is feasible to establish and develop DIC services in a developing country setting, Ethiopia. The study found that most of the common queries deal with drug interaction, therapeutic use, and general product information (most commonly about antimicrobials).

In Vitro and In Vivo Quality Evaluation of Glibenclamide Tablets Marketed in Addis Ababa, Ethiopia.

Good quality drugs fulfilling the regulatory parameters and produced per the current good manufacturing (CGMP) standards are very critical for best therapeutic outcome in patient therapy. Hence, this study assesses quality as well as physicochemical bioequivalence of five brands of glibenclamide tablets marketed in Addis Ababa using in vitro and in vivo methods. Friability, disintegration, dissolution, and assay for the content of active ingredients were evaluated using the methods described in the British Pharmacopeia (2009) and United States Pharmacopeia (2007). All the brands of glibenclamide tablets complied with the official specification for hardness, friability, disintegration, and assay. Difference factor (f1) values were less than 15 and similarity factor (f2) values were greater than 50 for all products of glibenclamide. The hypoglycemic effect of different products of glibenclamide tablets was evaluated on normoglycemic mice. The in vivo studies indicated that there is no significant difference in percent reduction of blood glucose level between the brands of glibenclamide and the innovator product (p > 0.05). Hence, based on the in vivo results and in vitro dissolution studies, the brands might be substituted with the innovator product in clinical practice.

Essential and toxic metals in tea (Camellia sinensis) imported and produced in Ethiopia.

Sixteen samples of packed tea leaves (Camellia sinensis) were purchased from supermarkets in Addis Ababa, Ethiopia for metal analysis. Elements were measured by FAAS and graphite furnace atomic absorption spectrometer (GFAAS) employing external calibration curves. The levels in mg/kg dried weight basis varied from Cu: 4.7-12.9; Cd: 0.02-2.83; Pb: <0.01-2.29; Zn: 8.6-198.3; Mn: 81.7-962.2; Al: 3376.4-10,369.3; K: 7667.7-10,775; Li: 0.2-0.62; Ba: 9.4-1407.1; Mg: 1145.6-1834.1; Fe: 286.4-880.9; Ca: 1414.2-2646.0; Na: 147.1-557.7. Levels of exposure to the investigated metals by drinking tea were checked with the recommended daily allowance (RDA) of the WHO/FAO. Considering the average daily consumption rate of tea alone, the possible daily intakes of Al, Ba and Mn surpass the amenability to the side effects associated with these elements like Alzheimer's disease, kidney damage and Parkinson's disease, respectively, for which drinking tea should cause awareness. The other investigated elements are in the acceptable range.

Utilization of Recently Established Drug Information Centers Located in the Public Hospitals of Addis Ababa, Ethiopia: An Assessment.

A drug information center is a unit designed for receiving, collecting, analyzing, and providing unbiased, accurate, and up-to-date information about drugs and their use. The drug information centers located in 4 public hospitals of Addis Ababa, Ethiopia, were assessed in this study. They received a total of 467 drug information queries during their functional period until the time of this study. Among these queries, only 409 were eligible to be included in the analysis. The majority of the queries were from public hospitals (69%), mostly from health care professionals (94.9%), out of which physicians were the highest (49.7%), followed by pharmacists (32.8%). The study found that the most frequently encountered requests were related to therapeutic use (17.3%), followed by general product information and product availability; the highest number of queries concerned the use of anti-infectives (29%).