Development of extended-release formulation of domperidone using a blend of Raphia hookeri gum and hydroxypropyl methylcellulose as tablet matrix

Purpose: To develop an extended-release formulation of domperidone using a blend of Raphia hookeri gum and hydroxypropyl methylcellulose as tablet matrix.Methods: Tablets (400 mg) containing 30 mg domperidone (DPD) were formulated using binary mixtures of hydroxypropyl methylcellulose (HPMC) and Raphia hookeri gum (RHG) as matrix former; and microcrystalline cellulose (MCC) as direct compression excipient. The proportions of the matrix formers (40 % of tablet weight) was varied as 100:0, 75:25, 50:50, 25:75 and 0:100. The composition of the matrix former was also kept constant (50:50) while MCC was varied as 40, 30, 20 and 10 %. The tablets were evaluated for compact density, tensile strength, friability and drug release over 24 h.Results: The tensile strength of tablets decreased while their friability increased with increase in the proportion of RHG. A similar trend was observed with decrease in the concentration of MCC. Tablets containing RHG alone as matrix former and 40 % MCC as direct compression excipient had tensile strength of 0.95 MNm-2, friability of 1.07 % and cumulative drug release of 83.2 % over a period of 24 h. Tablets containing equal proportions of HPMC and RHG as matrix former had the best release properties of 95.0 % over a period of 24 h.Conclusion: RHG is comparable with HPMC in terms of extending the release of  domperidone for a once daily administration. A suitable combination of the two  polymers for use as a matrix former is superior to either of the individual polymers.Keywords: Domperidone, Extended drug release, Hydroxypropyl methylcellulose, Raphia hookeri gum, Tablet propertie

Effect of polymer ratio on the quality of a co-processed excipient of prosopis gum and crab shell chitosan

Purpose: To assess the effect of polymer ratio on the quality of a novel co-processed excipient of prosopis gum and crab shell chitosan.Methods: The physicochemical properties (DSC thermogram, powder flow properties, porosity and swelling index as well as pH, viscosity and adhesive strength of 2 % w⁄v dispersions) of prosopis gum, chitosan and the three grades of co-processed excipient of prosopis gum and crab shell chitosan (Prosochit® 201, Prosochit® 101 and Prosochit® 102) were determined.Results: The three grades of the co-processed excipient of prosopis gum and crab shell chitosan (Prosochit®) were characterized by one endothermic transition each with peaks at 180 oC, 179 oC and 178 oC for Prosochit®201, Prosochit®101 and Prosochit®102 respectively. Flow properties increased with increase in proportion of chitosan. The porosity of the three grades of the new excipient was not significantly different from that of prosopis gum. Swelling indices of prosopis gum, chitosan, Prosochit® 201, Prosochit® 101 and Prosochit® 102 were 1135.53%, 14.00%, 726.33%, 677.33% and 514.00% respectively. The viscosity also decreased with increase in the proportion of chitosan. The new excipient had higher adhesive strength compared to the individual constituents (prosopis gum and crab shell chitosan).Conclusion: Prosochit® is superior to its individual constituents as a tableting excipient but its suitability for liquid formulation is reduced by increase in the proportion of chitosan.Keywords: Polymer ratio, Crab shell chitosan, Prosopis gum, Prosochit

Determination of Hydrophile - Lipophile Balance Value of Raphia hookeri Mann (Family: Palmae) Gum by Emulsification Method

Background: The hydrophile-lipophile balance (HLB) value is the major determinant of the applications of surfactants and any material that has potential for surface activity.Objective: To determine the HLB value of Raphia hookeri Mann (Family: Palmae) gum by emulsification method.Methods: Exudates of Raphia hookeri were collected and the gum was extracted and purified via dissolution in water, precipitation using ethanol, defatting using diethyl ether, oven-drying and pulverization. The pH and viscosity of 3 %w/v dispersion of the gum were determined in comparison with those of Tween 80 and Span 60. Series of emulsions were formed with the gum and Tween 80 as well as the gum and Span 60, in varying ratios of 1:5, 1:2, 1:1, 2:1 and 5:1. The emulsions were kept for 5 days at room temperature after which they were assessed for stability by checking the extent of creaming. The most stable emulsion was selected and the fractions of gum and standard surfactant incorporated were used for calculating the HLB value of the gum.Results: The pH of 3 %w/v dispersions was in the order: Raphia hookeri gum < Span 60 < Tween 80 while the viscosity of the dispersion of Raphia hookeri gum was found to be more than four folds higher than those of Span 60 and Tween 80. The most stable emulsion was found to be the one containing Raphia gum and Tween 80 in ratio of 5:1 and the HLB value of the gum was found to be 11.44.Conclusion: Raphia hookeri gum is more acidic and produces more viscous dispersion compared to Tween 80 and Span 60. The HLB value of the gum falls within the range of 8 - 16 which is characteristic of oil-in-water emulsifiers.Keywords: Raphia hookeri Mann, Gum, Hydrophile-lipophile balance, Emulsification

Emulsifying Properties of Hemicelluloses

This chapter focuses on the emulsifying properties of hemicelluloses. Hemicelluloses are gummy polysaccharides of complexity between gum and cellulose. Based on the major monosaccharide constituents of their backbone, hemicelluloses can be classified into xylans, mannans, xylogalactans and xyloglucans. Their sources include seeds, husks, straws, leaves and wood. Hemicelluloses bring about emulsification by viscosity modification and by formation of multilayered films around each globule of the dispersed phase. They have strong emulsifying power but are somehow limited by batch-to-batch variation and susceptibility to microbial and chemical degradations. These limitations are overcome by the use of purified and semisynthetic derivatives. Hemicelluloses and derivatives herein considered for their emulsifying properties include those from barley straw, wheat straw, corn fiber, locust bean, guar, soy bean, konjac, prosopis seed and afzelia seed. Hemicelluloses, as plant polysaccharides, are only second to cellulose in terms of abundance. They have superior emulsifying properties compared to the typical gums. They are amenable to many chemical modifications for the enhancement of stability and for the improvement of emulsifying properties. Hemicelluloses were not given adequate attention in the past; but this chapter shows that they are potentially useful emulsifying agents

Ex-vivo evaluation of crab shell chitosan as absorption enhancer in ciprofloxacin tablet formulation

This study was aimed at evaluating crab shell chitosan as absorption enhancer in ciprofloxacin tablet formulation using the ex-vivo model. Six batches of ciprofloxacin tablets containing varying concentrations of crab shell-derived chitosan ranging from 0 to 5% w/w at 1% w/w intervals were produced. Batch CTS-0 containing no chitosan served as the control. The crushing strength, friability, disintegration time, dissolution profile and permeation profile of all the batches were determined. Friability was not significantly affected but the crushing strength and disintegration time of tablets decreased with increase in concentration of chitosan. There was no significant difference in the cumulative percent drug released in 1 h but the cumulative percent drug permeated in 4 h increased with increase in the concentration of chitosan. It increased from 68% (when no chitosan was added) to 81.8% (when 5% w/w chitosan was incorporated). The polymer caused a faster onset of drug release but the eventual total drug released was not significantly influenced. It also improved the permeation of the released drug. This study correlates with in-vivo bioavailability study because the usual oral bioavailability of ciprofloxacin without absorption enhancer is 70%. Hence, crab shell chitosan at concentration of 5% w/w could increase the absorption of ciprofloxacin from 70 to 82%. The study suggests the use of the chitosan at this concentration to improve the absorption of ciprofloxacin.Key words: Crab shell chitosan, ciprofloxacin, dissolution, permeation, absorption

Lubricating Effects of Cocoa Butter and Coconut Oil in Conventional Paracetamol Tablets

Background: Due to chemical instability of some Active Pharmaceutical Ingredients often caused by magnesium stearate and its impurities, it is expedient to research into some other materials especially of natural origin, which would probably exhibit better lubricating activity, chemically inactive, less bioactive and less prohibitive.Objective: This work is designed to examine the lubricating properties of cocoa butter and coconut oil as alternative lubricants in comparison with conventional lubricant - magnesium stearate at different concentrations in paracetamol tablets.Materials and Methods: Cocoa butter was extracted from the seeds of Theobroma cacao and coconut oil from the meat of matured coconuts harvested from the coconuts palm (Cocos nucifera). Physicochemical evaluation was carried out on the extracted oils. Thirteen different formulations were prepared using different lubricants; magnesium stearate, cocoa butter and coconut oil at 0 – 4 %w/w concentrations. The prepared granules were evaluated for various pre-compression characteristics (bulk density, tapped density, angle of repose, Hausner’s quotient and Carr’s index) and post-compression characteristics (weight variation, friability, hardness, disintegration and dissolution times).Discussion: Most of the values obtained from the evaluation of pre- and post- compression characteristics correlate with the pharmacopoeial limits. The values of disintegration time were observed to increase as the lubricant concentration increased but no direct relationship with dissolution time. Tablet hardness values decreased while friability increased as the lubricant concentration increased for all the batches. From the study, cocoa butter and coconut oil at 2 – 4 % exhibited effective lubricating effect in the formulation of paracetamol tablet with respect to their values of weight variation, friability, hardness, disintegration and dissolution times.Conclusion: Cocoa butter and coconut oil could be employed as good alternative lubricants to the conventional ones in pharmaceutical tablet formulation.Keywords: Lubricants, Cocoa butter, Coconut oil, Magnesium stearate

INHIBITION OF GASTRIC DEGRADATION OF OMEPRAZOLE USING A pH-SENSITIVE POLYMER AS A BINDER IN TABLET FORMULATION

Objective: This work was aimed at formulating omeprazole tablets using afzelia gum as a binder that is capable of inhibiting the gastric degradation of the drug. Methods: Afzelia gum at different concentrations of 0, 5, 10, 15, 20 and 30% was used as a binder to formulate omeprazole tablets. The tablets were formulated by direct compression and the batches labelled F1 to F6 respectively. A batch containing 15% hydroxypropyl methylcellulose (F7) was also formulated. The tablets were characterized; and dissolution in a pH 1.2 dissolution medium over 120 min period was studied. Aliquots taken every 20 min were analyzed by ultraviolet spectrophotometry to determine the amount of drug released and not degraded. Results: Amounts of drug released and not degraded at time 120 min were 53.1%, 57.3%, 57.8%, 58.8%, 62.1%, 83.4% and 90.0% for F1 to F7 respectively. Conclusion: Afzelia gum at a concentration of 30% is suitable for use as a binder in tablet formulation of omeprazole to ensure substantial inhibition of gastric degradation of the drug

Dissolution and permeation characteristics of artemether tablets formulated with two gums of different surface activity

Purpose: To evaluate the dissolution and permeation characteristics of artemether tablets formulated with cashew and prosopis gums, and compare with tablets prepared with acacia gum.Methods: Artemether tablets containing varying concentrations (1.0 to 4.0 %w/w) of cashew and prosopis gums or 3 %w/w of acacia (control) gum as binders were formulated by wet granulation method. The tablets were evaluated for crushing strength, friability and disintegration time. Dissolution and permeation characteristics of the formulations were studied using USP methods.Results: Tablets formulated with prosopis gum had higher crushing strength, higher friability and higher disintegration time compared to those of cashew gum at corresponding binder concentrations. Tablets formulated with 3 %w/w cashew gum exhibited complete drug release within 1 h, 95 % drug permeation in 188 min (in simulated gastric fluid [SGF]) and 95 % permeation in 224 min (under simulated intestinal fluid [SIF] condition) while those made with 3 %w/w prosopis gum exhibited 70.7 % drug release in 1 h, 95 % permeation in 135 min (in SGF) and 95 % permeation in 170 min (under SIF condition).Conclusion: Cashew gum is effective as a binder over a relatively wide range of concentrations to achieve fast drug release though with minimal permeation enhancement while prosopis gum is characterized by delayed drug release but enhanced permeation of the released drug.Keywords: Cashew gum, Acacia, Prosopis, Artemether, Drug release, Dissolution, Permeatio

Polysorbate 80 – Modulated nanocrystallization for enhancement of griseofulvin solubility

Griseofulvin (GRFV1) is used in the treatment of many fungal infections, including ringworm and athlete’s foot, as well as fungal infections of the scalp, fingernails, and toenails. However, its bioavailability is limited by poor water solubility. This work was aimed at improving the aqueous solubility of the drug via Polysorbate 80 - modulated nanocrystallization. Two types of nanocrystals (GRFV3 and GRFV2) were generated, respectively, with and without the inclusion of Polysorbate 80 in the nanocrystallization process. The three forms of the drug were subjected to a flowability test, differential scanning calorimetry, Fourier transform infrared spectroscopy, particle size analysis, and aqueous solubility determination. The flowability of the particles was in the order GRFV3 > GRFV2 > GRFV1. The thermogram of the drug powder showed a sharp endothermic transition with a peak at 75 ºC; that of the nanocrystals GRFV2 showed a single sharp endothermic transition with a peak at 170 ºC, while that of GRFV3 showed two endotherms with peaks at 75 ºC and 164 ºC. The nanocrystallization with or without a surfactant did not result in any observable change in the chemical integrity of the drug. The mean particle size was in the order GRFV3 < GRFV2 < GRFV1. There was a significant difference (P < 0.0001) in the aqueous solubility of the three forms of the drug, with GRFV3 having the highest value. Polysorbate 80 - modulated nanocrystallization can increase the aqueous solubility of griseofulvin by 4.14 folds; it is a potential way of improving the bioavailability of the drug

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

Background: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. Methods: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. Findings: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. Interpretation: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic