Extraction, Characterization, and Evaluation of Lepidium sativum Linn. Mucilage as a Mucoadhesive Polymer.

Being biocompatible, less toxic, cheap, easily available, and environmentally friendly, there is an increased trust in natural polymers in the drug delivery system. Mucilages, among the natural polymers, are the primary metabolites of plants that have been widely utilized in pharmaceutical manufacturing for different purposes, and mucoadhesive is one among them. The present study was designed to investigate the use of LSM as a mucoadhesive polymer using ibuprofen as a model drug. The mucilage was extracted following an aqueous extraction method and its percentage yield was found to be 13.2% w/w. Besides, three microsphere formulations of ibuprofen were prepared using synthetic polymer hydroxyl propyl methyl cellulose (HPMC) K100M and the LSM in polymer to drug ratios of 1 : 1, 1 : 5, and 3 : 5 by applying ionotropic gelation followed by solvent evaporation methods. The microspheres were evaluated for various micromeritic properties and all the formulations exhibited free-flowing properties. Optical microscopic pictures of almost all the microspheres except F3 and F6 (which had more or less spherical shapes) were found to have irregular and discrete shapes. Besides, the surfaces of all the formulations were rough in texture. The drug entrapment efficiency of the microspheres was found to be between 52.08% ± 0.80 and 87.97% ± 0.72. The in-vitrowash-off test evidenced that almost 50 percent (especially F3) of the microspheres were able to adhere up to 18 h and showed remarkable bioadhesion properties. The in-vitro drug release profile indicated that all the formulations were able to prolong their drug release up to 12 h with a non-fickian release mechanism, except for F4, which followed a fickian release. Therefore, based on the findings of this study, LSM can be used as a potential alternative mucoadhesive excipient for sustained release formulations.

Physicochemical Characterization and Evaluation of the Binding Effect of Acacia etbaica Schweinf Gum in Granule and Tablet Formulations.

This study is aimed at evaluating the binding effect of Acacia etbaica gum in granule and tablet formulations using paracetamol as a model drug. Some physicochemical properties of the purified gum such as pH, the presence of tannin and dextrin, solubility, viscosity, loss on drying, total ash value, water solubility index, swelling power, moisture sorption, and powder flow properties were investigated. Paracetamol granules were prepared using wet granulation method at 2%, 4%, 6%, and 8% w/w of the Acacia etbaica gum and compared with granules prepared with reference binders (PVP K-30 and Acacia BP) in similar concentrations. The granules were characterized for bulk and tapped densities, compressibility index and Hausner ratio, angle of repose, flow rate, and friability. Finally, the prepared granules were compressed into tablets and evaluated for different tablet characteristics: weight uniformity, thickness, diameter, crushing strength, tensile strength, friability, disintegration time, and in vitro release profile. The physicochemical characterization revealed that tannins and dextrin are absent in the gum, and the gum has acidic pH. Both the moisture content and total ash values were within the official limits. Furthermore, the gum was found to be soluble in cold and hot water but insoluble in organic solvent and exhibited a shear thickening viscosity profile and excellent flow properties with excellent compressibility. The granules prepared with the gum of Acacia etbaica and reference binders showed good particle size distribution and excellent flow and compressibility properties. All the prepared tablets passed pharmacopeial specifications with respect to their uniformity of weight, thickness, and disintegration time. Tablets formulated with Acacia etbaica gum and acacia BP meet the compendial specification for friability at binder concentrations more than 2%. Drug release properties of all the batches formulated with Acacia etbaica, PVP, and acacia BP complied with the pharmacopeial specification. It can be concluded that the gum of Acacia etbaica could be explored as an alternative excipient for its binder effect in granule and tablet formulations.

Evaluation of Grewia ferruginea Hochst ex A. Rich Mucilage as Suspending Agent in Metronidazole Benzoate Suspension.

Various species of the genus Grewia have been investigated for different pharmaceutical applications as excipients, yet a study on the potential use of Grewia ferruginea mucilage (GFM) as a suspending agent is lacking. Thus, this study is aimed at evaluating the efficacy of Grewia ferruginea mucilage (GFM) as a suspending agent in metronidazole benzoate suspension. The suspensions were prepared using 0.5%, 1%, 1.5%, and 2% w/v of GFM and compared with suspensions prepared from xanthan gum (XGM) and sodium carboxyl methyl cellulose (SCMC) in similar concentrations. The prepared suspensions were evaluated for visual appearance, pH, rheology, sedimentation volume, redispersibility, degree of flocculation, and in vitro drug release profile. Stability study was done at different storage conditions for three months. The results indicated that all the prepared suspension formulations exhibited pseudoplastic flow characteristics with viscosity imparting ability of the suspending agents in the order of XGM > GFM > SCMC (p < 0.05). The flow rate and redispersibility of the formulations prepared with GFM were significantly lower than those with SCMC and higher than those prepared with XGM. At 0.5% w/v suspending agent concentrations, the sedimentation volume of the formulations was in the order of XGM > GFM > SCMC (p < 0.05). However, at all other concentrations, the sedimentation volume of the formulations prepared with GFM had similar results with XGM but exhibited significantly higher sedimentation volume than SCMC. The formulations with GFM showed a higher degree of flocculation at 0.5% w/v concentration but were comparable at 1.5% w/v with XGM containing formulations. The pH, assay, and in vitro release profile of all assessed formulations were within the pharmacopial limit. Thus, based on the finding of this study, it can be concluded that Grewia ferruginea bark mucilage has the potential to be utilized as a suspending agent in suspension formulations.

Safety and Biopharmaceutical Challenges of Excipients in Off-Label Pediatric Formulations.

BACKGROUND: One of the major challenges in pediatric treatment is the lack of suitable drug preparations specifically designed and marketed for children. Most of the FDA approved drug formulations for adults have not been approved for use in pediatric patients. Shortage of suitable pediatric dosage information often leads health professionals to use adult formulations in an off-label manner. The aim of this work was to review the safety and biopharmaceutical challenges of commonly found excipients in off-label pediatric formulations as well as to show the current progress to alleviate pediatric toxicity related to excipients. METHODS: Research findings and medical case reports were searched from credible sources including Scopus, PubMed, OVID, Google Scholar, Embase, Cochrane Library, and Web of Science. RESULTS: As several studies and clinical case reports have revealed, off-label adult formulations usage causes pediatric patients to become exposed to potentially harmful excipients, which are essential components of drug products. In addition to their toxicities, some of the excipients affect the biopharmaceutical property of different drugs. Immature organ and body composition, large body surface area and slower metabolism and elimination capabilities of pediatrics are the main causes of toxicities associated with different excipients. Recent studies have also shown that good progress is being made to develop safe and suitable excipients for pediatric use. CONCLUSION: A risk and benefit assessment should be done before using off-label formulation as excipients cause mild to severe toxicities and biopharmaceutical problems to pediatric patients.

The Effect of Coffee on Pharmacokinetic Properties of Drugs : A Review.

BACKGROUND: Coffee has been the most commercialized food product and most widely consumed stimulant beverage in the world. It is a major source of caffeine which is the most bioactive component of coffee. Although both the United States Department of Agriculture and European Food Safety Authority consider daily intake of coffee which contains 400 mg of caffeine as safe for health, it causes different clinically significant pharmacokinetic interactions with many drugs. The aim of this work was to review the effect of coffee on the pharmacokinetic properties of drugs. METHOD: This review was done by investigating the in vitro and in vivo research findings, clinical case reports, and expert panels from credible sources including Scopus, PubMed, Hindawi, OVID, Google Scholar, Embase, Cochrane Library, and Web of Science. RESULT: Several studies and medical case reports evidently showed that concomitant consumption of coffee significantly affects the absorption, distribution, metabolism, and excretion of many drugs. These effects of coffee on the pharmacokinetics of drugs could lead to enhanced therapeutic response, therapeutic failure, or toxic reactions. Conclusion and Recommendation. Concomitant use of coffee should be avoided with medications which have a significant interaction with coffee. There should be an appropriate time gap between intake of drugs and coffee based on drug properties. Pharmacists and clinicians should be aware of the potential risks of drug-coffee interaction and advice patients appropriately. Further in vitro and in vivo studies should be done for frequently prescribed drugs to get a strong evidence on the pharmacokinetic interaction with coffee.

Physicochemical Characterization of Grewia ferruginea Hochst. ex A. Rich Mucilage for Potential Use as a Pharmaceutical Excipient.

Gum and mucilages from natural sources are in recent times increasingly investigated for pharmaceutical applications. Different studies have shown that the gum and mucilage fraction of various species of the genus Grewia were found to be effective viscosity enhancers, stabilizers, disintegrants, suspending agents, gelling agents, bioadhesives, film coating agents, and binders. However, no study has been conducted on the potential use of Grewia ferruginea mucilage (GFM) as a pharmaceutical excipient. Therefore, this study was aimed at characterizing the Grewia ferruginea bark mucilage for its potential use as a pharmaceutical excipient. The mucilage was extracted from the Grewia ferruginea inner stem bark through aqueous extraction, precipitated with 96% ethanol, dried, and powdered. The powdered mucilage was characterized for different physicochemical properties such as powder property, loss on drying, solubility and swelling index, ash value, pH, viscosity, moisture sorption property, microbial load, and acute oral toxicity. According to the results, the percentage yield of the final dried and powdered GFM was found to be 11.96% (w/w). The density and density-related properties of the mucilage showed good powder flow property. The GFM exhibited pseudoplastic flow behavior. Moisture sorption property of GFM revealed its hygroscopic nature, and its solubility and swelling property was increased with temperature. The pH of GFM was near neutral. Microbial load of the mucilage was within the pharmacopoeial limit, and the oral acute toxicity test revealed that the mucilage is safe up to 2000 mg/kg. From the investigations of this study, it can be concluded that Grewia ferruginea bark mucilage has the potential to be utilized as an excipient in pharmaceutical formulations.

Preparation, Optimization, and Evaluation of Epichlorohydrin Cross-Linked Enset (Ensete ventricosum (Welw.) Cheeseman) Starch as Drug Release Sustaining Excipient in Microsphere Formulation.

Ensete ventricosum (Welw.) cheeseman which belongs to the family of Musaceae is one of the main sources of starch in Ethiopia. This study aimed at evaluating epichlorohydrin cross-linked enset starch as a drug release sustaining excipient in microsphere formulations of theophylline. Extracted enset starch was cross-linked using epichlorohydrin as a cross-linking agent. The effect of cross-linker concentration, cross-linking duration, and cross-linking temperature on the degree of cross-linking and release rate of microspheres prepared by emulsion solvent evaporation method was investigated using the two-level full factorial design. Accordingly, the concentration of epichlorohydrin and duration of cross-linking were the most significant factors affecting both the degree of cross-linking and drug release rate. Thus, the effects of these two factors were further studied and optimized using the central composite design. As per the numerical method of central composite design, the optimal points were obtained at epichlorohydrin concentration of 13.70% and cross-linking time of 3.82 h. Under these optimal conditions, the model predicts the degree of cross-linking of 74.70% and drug release rate of 28.00 h1/2. The validity of these optimal points was confirmed experimentally. The microspheres of the optimum formulation also exhibited minimum burst release with sustained release for 12 h. Besides, the optimized formulation followed the Higuchi square root kinetic model with non-Fickian diffusion release mechanism. The finding of this study suggested that cross-linked enset starch can be used as an alternative drug-release-sustaining pharmaceutical excipient in microsphere formulation.

Evaluation of Acid-Modified Ethiopian Potato (Plectranthus edulis) Starch as Directly Compressible Tablet Excipient.

Ethiopian potato is one of the tuber-bearing members of the family Lamiaceae. It is an indigenous crop in Ethiopia and important source of starch. Unprocessed native starches are structurally weak and functionally restricted for application in pharmaceutical technologies. Consequently, starch is usually modified either chemically or physically to make it convenient for industrial use. The aim of the study was to prepare and characterize acid-modified Ethiopian potato starch (AMEPS) and evaluate its functionality as a direct compressible excipient in tablet formulations. The extracted starch from Ethiopian potato tuber was modified using 6% HCl concentration for 8 days, then dried using oven and spray drying techniques, and subsequently evaluated and compared with the native Ethiopian potato starch (NEPS) and S1500® as a direct compressible excipient. Acid modification of the NEPS decreased the moisture content and swelling power while increased the percent solubility. The X-ray diffraction revealed that both the NEPS and AMEPS have B-type crystal patterns. The AMEPS showed improved flowability compared to the NEPS. This improvement was further enhanced by the spray drying process. The compactability study revealed that the tensile strength of spray-dried AMEPS (16.76 kg/cm2) was significantly higher than that of the spray-dried NEPS (7.07 kg/cm2) and S1500® (11.66 kg/cm2). The AMEPS was less sensitive to lubricants compared to the NEPS and Starch 1500®. Similarly, the dilution potential of the AMEPS was superior to the NEPS and S1500®. The AMEPS accommodated up to 50% of paracetamol while the NEPS and S1500® were able to hold only up to 30%. Pharmacopoeial specifications for disintegration and dissolution were met by the paracetamol tablets prepared by AMEPS. Thus, considering all the results obtained, spray-dried AMEPS could be a potential alternative directly compressible tablet excipient.

Formulation and Optimization of Monolithic Fixed-Dose Combination of Metformin HCl and Glibenclamide Orodispersible Tablets.

The treatment of type II DM involves the use of combination of drugs, especially at the chronic stage. However, the pill burden of this combination therapy combined with swallowing difficulties, occurring at a later stage of DM, has been the major challenge for successful treatment outcomes. This study was aimed at formulating and optimizing a monolithic fixed-dose combination (FDC) of metformin (MET) and glibenclamide (GLB) orodispersible tablets (ODTs) to overcome both the pill burden and swallowing problems. The FDC ODTs were prepared by the melt granulation technique using polyethylene glycol (PEG) 6000 as a binding agent and crospovidone as a superdisintegrant. In the preliminary study, the effects of sodium lauryl sulphate (SLS), PEG 6000, crospovidone, and compression force on friability, disintegration time, and drug release of tablets were investigated. The FT-IR studies showed that there were no incompatibilities between MET and GLB as well as within excipients. The preliminary studies revealed that PEG 6000 and compression force significantly affect both the friability and the disintegration time, while SLS and crospovidone only affect the disintegration time. Therefore, the effects of PEG 6000, crospovidone, and compression force were further studied and optimized using the central composite design. Accordingly, the most desirable optimal values were obtained at 3.82% of PEG 6000, 9.83% of crospovidone, and 10.6 kN compression force having a friability of 0.302% and a disintegration time of 18.7 seconds. From these results, it can be concluded that a monolithic FDC of MET and GLB ODTs having adequate mechanical strength and faster disintegration time was successfully formulated.

Availability and affordability of priority life-saving medicines for under-five children in health facilities of Tigray region, northern Ethiopia.

BACKGROUND: In developing countries, child health outcomes are influenced by the non-availability of priority life-saving medicines at public sector health facilities and non-affordability of medicines at private medicine outlets. This study aimed to assess availability, price components and affordability of priority life-saving medicines for under-five children in Tigray region, Northern Ethiopia. METHODS: A cross-sectional study was conducted in Tigray region from December 2015 to July 2016 using a standard method developed by the World Health Organization and Health Action International (WHO/HAI). Data on the availability and price of 27 priority life-saving medicines were collected from 31 public and 10 private sectors. Availability and prices were expressed in percent and median price ratios (MPRs), respectively. Affordability was reported in terms of the daily wage of the lowest-paid unskilled government worker. RESULTS: The overall availability of priority life-saving drugs in this study was low (34.1%). The average availabilities of all surveyed medicines in public and private sectors were 41.9 and 31.5%, respectively. The overall availability of medicines for malaria was found to be poor with average values of 29.3% for artemisinin combination therapy tablet, 19.5% for artesunate injection and 0% for rectal artesunate. Whereas, the availability of oral rehydration salt (ORS) and zinc sulphate dispersible tablets for the treatment of diarrhea was moderately high (90% for ORS and 82% for zinc sulphate). Medicines for pneumonia showed an overall percent availability in the range of 0% (ampicillin 250 mg and 1 g powder for injection and oxygen medicinal gas) to 100% (amoxicillin 500 mg capsule). The MPRs of 12 lowest price generic medicines were 1.5 and 2.7 times higher than the international reference prices (IRPs) for the private and public sectors, respectively. About 30% of priority life-saving medicines in the public sector and 50% of them in the private sector demanded above a single daily wages to purchase the standard treatment of the prevalent diseases of children. CONCLUSIONS: The lower availability, high price and low affordability of lowest price generic priority life-saving medicines in public and private sectors reflect a failure to implement the health policy on priority life-saving medicines in the region.

Prescription drug use during pregnancy in Southern Tigray region, North Ethiopia.

BACKGROUND: Judicious utilization of drugs rescues the fetus from the harmful effects while treating the health problems of the pregnant women. This study aimed at evaluating drug utilization pattern and its associated factors among pregnant women in Southern Tigray, Ethiopia. METHOD: Institution based cross-sectional study was conducted among 647 pregnant women who had been attending obstetrics-gynecology and antenatal care units in different health facilities of Southern Tigray region. The study participants were selected using multistage sampling technique. Data collection was done using pre-tested semi-structured questionnaires and by reviewing antenatal follow-up cards. Descriptive and inferential statistics were analyzed, to assess drug utilization pattern and its associated factors among pregnant women, using SPSS version 20 software. RESULTS: Of 647 pregnant women, 87.5% were prescribed with at least one medication. As per the United States Food and Drug Administration (US-FDA) risk classification system, 87.7, 7.9, 3.9, and 0.5% of the prescribed drug were from category A, B, C and D, respectively. Prescription drug use was more likely among gynecology ward visitors [AOR = 8.97, 95% Cl (2.69-29.88)] and among those who visited health facilities for the first time during their first [AOR =2.65, 95% Cl (1.44-4.84)] and second [AOR = 2.50, 95% Cl (1.36-4.61)] trimesters. CONCLUSION: Majority of the study population used safe and appropriate medications according to US-FDA risk classification system, with the exception of low proportion (0.5%) of medication with potential risk for the fetus. The average number of drug prescribed per pregnant women was in the recommended range of WHO drug use indicators guideline.

Late presentation for diagnosis of HIV infection among HIV positive patients in South Tigray Zone, Ethiopia.

BACKGROUND: In spite of the availability and accessibility of HIV testing opportunities and efforts, people are being late to test in the course of HIV infection. Late diagnosis leads to late anti-retroviral therapy initiation which in turn results in poor treatment outcome and prognosis of the disease. The aim of this study was to determine the prevalence and predictors of late HIV diagnosis among HIV-infected patients in South Tigray Zone, Ethiopia. METHODS: A facility based cross sectional study was conducted among HIV positive patients from February 1-30, 2014 in Southern Tigray, Ethiopia. Multistage sampling technique was employed to select the study participants. Data were collected by reviewing patient medical card and interviewing using structured questionnaire. Data were entered using Epi-Data version 3.1 and analyzed using SPSS version 20.0. Both bivariate and multivariate logistic regressions were modeled to evaluate the association of predictors with late diagnosis of HIV infection. RESULTS: Out of 789 study participants, 68.8 % of them were late for HIV diagnosis. Feeling healthy (65.7 %), fear of stigma and discrimination (32.4 %) and using traditional treatment (1.5 %) were reported as the main reasons for late HIV diagnosis. Use of Khat [AOR = 3.27, 95 % CI (1.75, 6.13)], bed ridden functional status [AOR = 2.66, 95 % CI (1.60, 4.42)], ambulatory functional status [AOR = 1.56, 95 % CI (1.03, 2.35)] and Muslim religion [AOR = 2.26, 95 % CI (1.13, 4.49)] were significantly associated with late presentation for HIV diagnosis. CONCLUSIONS: High prevalence of late HIV diagnosis was recorded in Southern Tigray Zone, Ethiopia. Public health educations and campaigns targeted at improving early diagnosis and prognosis of people living with HIV/AIDS in Southern Tigray, Northern Ethiopia should be underway.

Drug Use during Acute Illness in Tigray Region, Northern Ethiopia: A Household Study.

BACKGROUND: Drug use study in the community enables health authorities to understand pattern of drug utilization and its related aspects. This, in turn, can help to develop rational drug policies to be harmonized in accordance to the need of the community. OBJECTIVE: The aim of this study was to assess drug use during acute illness by the general population in Tigray region, Northern Ethiopia. METHOD: A community based cross-sectional study was undertaken in April 2013 in Tigray Region, Ethiopia. A total of 1034 households were interviewed in the study. A multi-stage sampling technique was used to select households. Data were collected using a pre-tested structured questionnaire. Data were analyzed using descriptive statistics and bivariate and multivariate logistic regression model. RESULTS: Out of 1000 households, 210(21%) reported an episode of acute illness. The prevalence of acute illnesses in rural areas 126(25%) (AOR = 1.83, 95% CI: 1.21-2.76) was significantly higher than that of urban areas 84(17%). Cough, runny nose, sore throat, earache, fever and headache added up to 155(52%) of all reported symptoms of acute illnesses. The majority of the patients 162 (77%) took modern medications for the managements of their diseases. Half 105(50%) of the consumed medications were antibiotics. The large proportions 173(83%) of medicines for acute illness were taken orally. The greater proportions 150(93%) of medications were prescribed by health professionals. Thirty-four households (21%) reported treatment discontinuation. CONCLUSION: The prevalence of acute illnesses in this study was found to be 21%. Acute illnesses were more common in rural areas than urban areas. Antibiotics were the most frequently used drugs for acute illnesses.

Household Storage of Medicines and Associated Factors in Tigray Region, Northern Ethiopia.

INTRODUCTION: The presence of medicines in households is a risk factor for irrational drug use. This study aimed at investigating the prevalence and factors associated with home storage of medicines in Tigray Region, Ethiopia. METHOD: A community based cross-sectional study was conducted in April 2013 in Tigray Region, Ethiopia. A total of 1034 participants were enrolled in the study. A multi-stage sampling method was employed to select households. Data were collected with the help of a pre-tested structured questionnaire and analyzed using descriptive statistics and bivariate and multivariate logistic regression. RESULT: Of the total households visited, 293(29%) stored drugs. The mean number of drugs per household was 1.73. The most common classes of drugs found in households were analgesics 149(29%) and antibiotics 128(25%). Most of the medicines kept in households were used for ongoing treatments 316(62%) and available in tablet dosage form (70%). More than half of the medications kept at homes were not adequately labeled while drawer 180(36%) were reported as the main place of drug storage. The proportion of home storage of medicines in rural area (AOR = 0.56, 95% CI: 0.39-0.81) was lower than that of urban area. However, households having family member(s) working in health facilities (AOR = 2.03, 95% CI: 1.09-3.77) were associated with an increased home storage of medicines. CONCLUSION: Most drugs kept at home were not appropriately labeled and stored in a safe place. Residence area (rural versus urban) and the presence of health professional(s) in the households affects household drug storage. Hence, public education campaign should be considered as an intervention to improve the storage condition of medicines in the households.