SIMPLE HPLC VALIDATED METHOD FOR THE DETERMINATION OF DILTIAZEM HYDROCHLORIDE IN HUMAN PLASMA

Objectives: To develop and validate a high-performance liquid chromatographic method for determination of diltiazem hydrochloride (DLZ) in human plasma. Methods: Mixture of n-hexane and 2-propanol (96:4, ratio) was added to plasma at sample preparation time followed by centrifuging the samples. The obtained upper organic layer was transferred and evaporated to dryness. The residue was reconstituted with a mobile phase and the supernatant was then injected onto the column. The mobile phase used was consisted of 0.2 M ammonium dihydrogen phosphate, acetonitrile, isopropyl alcohol and triethylamine (55:43:1.7:0.3, v/v) with pH adjusted to 4.5 using 85% phosphoric acid. The flow rate was 0.7 ml/min. UV detector set at 240 nm and samples were quantified using peak area. Results: A well-resolved DLZ peak and free of interference from endogenous compounds in plasma with a retention time of 6.03 min was achieved. Recovery of DLZ was satisfactory (‰¥ 91.3%) over the concentration range tested 0.25 - 20 µg/ml. LOD of this assay was 0.125 µg/ml and LOQ was 0.25 µg/ml and, at this concentration, intra- and inter-day CV were 6.8 and 9.2 %, respectively. DLZ was found to be stable in plasma after storage at -80 ºC, over 90 days. Conclusion: The HPLC method described in this article was simple, sensitive, selective, reproducible, linear, precise, accurate, stability indicating and requires only a small sample volume, lending it suitable for the determination of DLZ concentration in routine measurements for pharmacokinetic/bioavailability studies

THE ASSOCIATION OF TYPE 2 DIABETES WITH OBESITY AND OTHER FACTORS: IN MULTINATIONAL COMMUNITY

Objective: Quantifying the influence of Obesity and other contributing factors on inducing Type 2 Diabetes is important to allow for rational planning and allocation of resources. Therefore, the major aim of this study was to estimate theinfluence of obesity on inducing Type 2 Diabetes and explore the relationship between Type 2 Diabetes and different contributing factors such as age, gender, race, type of food taken and family history in a many healthy and non-healthy human multinational volunteers in the United Arab Emirates. Methods: A stratified cross-sectional analysis observational study was conducted on 800 healthy males and non-pregnant female volunteers aged between 18 and 45 years old. A Structured Investigational Assessment (SIA) as a principle of analysis was used to find out the contributing factors and correlations between obesity and Type 2 Diabetes. SIA was well designed and highly structured to allow the same types of information to be collected from a large number of people in the same way and for data to be analyzed quantitatively and systematically. Information obtained from volunteers contained age, race, gender, weight, height, quality of food taken, smoking status, medical conditions, emotional, material and physical activity status. Pearson's chi square test was used to study the significance of different contributing factors and obesity on inducing Type 2 Diabetes. Results: Results indicated a significant difference that was found between the presences of Type 2 Diabetes in obese volunteers compared to non-obese volunteers regardless, age, race, and gender. However, analysis showed that gender, age, race, family history with Type 2 Diabetes and quality of food taken as one of the contributed factors that can induce Type 2 Diabetes, even in the non-obese adults. Conclusion: Our findings revealed that female, Middle Eastern and obese people who consume non-healthy food are at higher risk for developing Type 2 Diabetes. This can be attributed to the lack of awareness and public health education. Therefore,the prevalence of Type 2 Diabetes is high among the United Arab Emirates population and represents a major clinical and public health problem. A national prevention program to prevent diabetes and address the modifiable risk factors at the community level, targeting high-risk groups, should be implemented

DETERMINATION OF NIFEDIPINE IN RAT PLASMA USING HPLC-UV DETECTOR: A SIMPLE METHOD FOR PHARMACOKINETICS AND ORAL BIOAVAILABILITY STUDIES

Objective: To develop and validate a high-performance liquid chromatographic method (HPLC) for the determination of nifedipine (NFD) concentration in rat plasma.Methods: 1.5 mol of sodium hydroxide solution was added to each plasma sample, followed by the addition of an extraction solvent based on n-hexane and dichloromethane (70: 30, v/v). The organic layer was transferred and evaporated to dryness under nitrogen flow. The residue was reconstituted with 0.5 mol of acetic acid, followed by the addition of n-hexane. After centrifuging the mixture, the supernatant organic layer of n-hexane was discarded, and the aqueous solution was injected onto the HPLC using A Phenomenex Luna-C18 reversed phase analytical column (250 x 4.6 mm, 5 µm). The mobile phase consisted of 0.01 mol aqueous ammonium formate: methanol: acetonitrile (55: 43: 2, v/v) with pH adjusted to 4.9 using formic acid. The flow rate was 0.8 ml/min; UV detector set at 235 nm and the samples were quantified using the peak area.Results: A well-resolved NFD peak was achieved free of interference from endogenous compounds in rat plasma. Recovery of NFD was more than 93 % over concentrations ranged from 5.00 to 200 ng/ml. The limit of quantification (LOQ) of this assay was 6 ng/ml and, intra-and inter-day coefficient of variation (CV) were 5.75 % and 7.93 %, respectively. NFD was found to be stable in rat plasma after being stored at -30 °C over 90 d.Conclusion: The stability, sensitivity, specificity and reproducibility of this method make it suitable for the determination of NFD plasma concentration in pharmacokinetics and oral bioavailability studies

Transdermal patches: Design and current approaches to painless drug delivery

Use of transdermal patches can evade many issues associated with oral drug delivery, such as first-pass hepatic metabolism, enzymatic digestion attack, drug hydrolysis and degradation in acidic media, drug fluctuations, and gastrointestinal irritation. This article reviews various transdermal patches available in the market, types, structural components, polymer role, and the required assessment tools. Although transdermal patches have medical applications for smoking cessation, pain relief, osteoporosis, contraception, motion sickness, angina pectoris, and cardiac disorders, advances in formulation development are ongoing to make transdermal patches capable of delivering more challenging drugs. Transdermal patches can be tailored and developed according to the physicochemical properties of active and inactive components, and applicability for long-term use. Therefore, a number of chemical approaches and physical techniques for transdermal patch development are under investigation

Butylglyceryl pectin nanoparticles: synthesis, formulation and characterization

Pectin is a polysaccharide with very good gel forming properties that traditionally has found important applications in foods and pharmaceutical industries. Although less studied, chemical modifications of pectin leading to a decrease in its hydrophilicity can be useful for the development of novel drug carriers. To this aim, butylglyceryl pectins (P-OX4) were synthesized via functionalization with n-butylglycidyl ether and subsequently formed into nanoparticles. Chromatographic, spectroscopic, and thermal analytical methods were employed to characterize the novel butylglyceryl pectins (P-OX4) obtained, prior to their formulation into nanoparticles via nanoprecipitation. Nuclear magnetic resonance (NMR) and Fourier transform infrared (FT-IR) spectroscopy confirmed a degree of modification in these materials in the range 10.4−13.6%, and thermal stability studies indicated an increase in both the thermal decomposition onset and glass transition temperature values (compared to those of the original pectin). An increase in the molecular weight and a decrease in the viscosity of P-OX4, when compared to the starting material, were also observed. The resulting nanoformulations were investigated in terms of particle morphology, size and stability, and it was found that particles were roughly spherical, with their size below 300 nm, and a negative zeta potential (−20 to −26 mV, indicating good stability). Having demonstrated the ability to load Doxorubicin at the level of 10%, their potential in drug delivery applications warrants further investigations

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

APPROACHES TO ACHIEVE AN ORAL CONTROLLED RELEASE DRUG DELIVERY SYSTEM USING POLYMERS: A RECENT REVIEW

The present article contains a brief review of various formulation approaches used in controlled release drug delivery systems, the role of polymers in the controlled delivery of many fast release drugs and the mechanism of drug release from these polymeric matrices. The oral controlled release system of many drugs has been known to be an essential part of formulation development in drug delivery systems. It has been the focus of pharmaceutical research for many years due to its various advantages over conventional dosage forms. Administering the drug for release in the blood at a controlled rate, to maintain relatively constant drug levels in plasma over a controlled period of time, can overcome many problems associated with conventional dosage forms. The applicability of these dosage forms is due to reduction in the frequencies of drug dosing, which lead to patient convenience and compliance. In addition, a reduction of wide fluctuations in plasma drug concentration peak can be obtained. As a result, toxicity and poor efficacy can be avoided, especially with drugs of narrow therapeutic indices. Such problems, associated with conventional dosage forms of many drugs, can be overcome by using controlled release drug delivery systems, to deliver the drug for absorption at a controlled rate over an extended period of time. The controlled release dosage form should be tailored so that variations in the components can lead to predictable alterations in the drug release profiles. Various controlled release drug delivery systems have different mechanisms to control the drug release rate, such as the osmotic pump, ion exchange resin and matrix systems which have been widely utilized as controlled release drug delivery approaches. Besides, polymers have often been used in the components of controlled release drug delivery systems. A sustained release profile, without occurring of the dose dumping, and sufficient bioavailability can be achieved when a drug is embedded in some polymeric materials such as gelucires.Â

COMPARISON BETWEEN GENERIC DRUGS AND BRAND NAME DRUGS FROM BIOEQUIVALENCE AND THERMOEQUIVALENCE PROSPECTIVE

The belief that generic drugs are inferior to brand name drugs has been always under debate. Especially since the price of generic drugs is generally far cheaper than brand-name drugs. Although, this is because of waiving the preclinical studies and clinical trials for the generic drug, the quality, and purity of materials used for generic drug preparation is still arguable. Thus, the objective of this overview was to find out the tolerable deviations between generic and brand name drugs which should not alter the pharmacology. Using inactive additives in the generic drug different than in the brand name drug, such as binders, glidants, diluents, anti-adherents, disintegrants or polymer carrier material and filler should not change the drug bioavailability and pharmacokinetic parameters as long as both products using the identical active ingredient(s) in equivalent amounts. Even if both drug products are bioequivalent to each other in terms of active ingredient, they are not in terms of inactive ingredients. Hence, the probability of unexpected adverse drug reaction and allergies from the generic formulation are possible, especially, when people react sensitive toward specific component. Therefore, the occasional negative response occurring upon the switch from brand-name drug to the generic drug can be attributed to intra-and inter-patient variations toward inactive ingredients. Variations toward inactive ingredients can be obtained experimentally by utilizing a proper thermoanalytical technique. As a result, thermoequivalence of generic drugs to brand name drugs can be determined based on thermal information obtained from both products. In conclusion, thermoequivalence study can be a useful tool to demonstrate any possible variation between the inactive ingredients of both products

Mixed micelles loaded with bile salt : an approach to enhance intestinal transport of the BCS class III drug cefotaxime in rats

Cefotaxime is a class III drug according to the Biopharmaceutical Classification System due to low intestinal permeability based on poor oral bioavailability. Bile salt compounds have been shown to be effective additive for drug permeation through several biological membranes. The main purpose of this study was to investigate the ability of a mixed micelles made of phosphatidylcholine, sodium deoxycholate, and loaded with a cefotaxime-3α,7α-dihydroxy-12-keto-5β-cholanate complex to enhance the oral bioavailability of cefotaxime in rats