Administration Compliance Research Articles

TAX ADMINISTRATION AND VOLUNTARY COMPLIANCE: A STUDY OF SELECTED STATE INTERNAL REVENUE SERVICE IN SOUTH-WEST NIGERIA

This study examined the effect of tax administration and voluntary compliance of selected State Internal Revenue Service in Nigeria. The field survey research method was adopted for the study. Primary data obtained through the administration of structured questionnaire were used to test the hypotheses using regression analysis. The population of the study consisted of 4499 members of staff in tax revenue offices in South-west Nigeria. Three hundred and eighty-seven copies of questionnaires were administered while 382 (98.7%) were retrieved. The findings of the study revealed that tax administration of the selected Sate Internal Revenue Services has a significant effect on voluntary compliance (Adj.R2 = 0.160, F(3, 383) = 25.113, p < 0.05). The study concludes that Tax administration measured as Tax assessment (TASS), Tax remittance (TREM) and Tax collection (TCOL) had a significant effect on the Voluntary Compliance of taxpayers of selected State Internal Revenue Services in South-west Nigeria. The study recommends that State tax authorities should restructure their tax administration system in order to increase their efficiency and effectiveness in tax assessment, tax collection and tax remittance. This will make taxpayers voluntarily pay their taxes without using means of enforcements. Also, the State tax authorities should embark on training its staff on tax collections and not completely rely on the external agents in tax collections.

Formulation and Evaluation of Mebeverine Hydrochloride Sustained Release Capsules by Pelletization Technique

The objective of the present study is aimed to formulate and evaluate sustained-release Mebeverine hydrochloride capsules using the Pelletization technique. Mebeverine hydrochloride, an anti-spasmodic drug is highly water soluble with a half-life of 2h and is suitable to develop sustained action for the treatment of irritable bowel syndrome. Mebeverine hydrochloride prolongs medication release in the GIT and, as a result, into the plasma, while reducing the frequency of drug administration, adverse effects, and patient compliance. Mebeverine hydrochloride were prepared by using polymers The drug-polymer and excipient compatibility was defined by the FTIR studies in the pre-formulation study. The calibration curve for the drug is plotted and checked the physicochemical properties. Six formulations (F1-F6) of Mebeverine hydrochloride pellets were prepared using different quantities of Ethylcellulose N 50 and other standard excipients. In vitro, drug release studies were performed for the pellets for 1.2, 4, 6, 8, and 12hrs. The optimized formulation F6 showed 76.8 % drug release after 12h showing that ethyl cellulose N 50 acts as a rate-controlling agent. The drug release of the chosen formulation follows first-order kinetics with a zero-order mechanism, according to absorption kinetics.

Mucoadhesive carriers for oral drug delivery.

Among the various dosage forms, oral medicine has extensive benefits including ease of administration and patients' compliance, over injectable, suppositories, ocular and nasal. Despite of extensive demand and emerging advantages, over 50% of therapeutic molecules are not available in oral form due to their physicochemical properties. More importantly, most of the biologics, proteins, peptide, and large molecular drugs are mostly available in injectable form. Conventional oral drug delivery system has limitation such as degradation and lack of stability within stomach due to presence of highly acidic gastric fluid, hinders their therapeutic efficacy and demand more frequent and higher dosing. Hence, formulation for controlled, sustained, and targeted drug delivery, need to be designed with feasibility to target the specific region of gastrointestinal (GI) tract such as stomach, small intestine, intestine lymphatic, and colon is challenging. Among various oral delivery approaches, mucoadhesive vehicles are promising and has potential for improving oral drug retention and controlled absorption to treat local diseases within the GI tract, as well systemic diseases. This review provides the overview about the challenges and opportunities to design mucoadhesive formulation for oral delivery of therapeutics in a way to target the specific region of the GI tract. Finally, we have concluded with future perspective and potential of mucoadhesive formulations for oral local and systemic delivery.

Alginate-Based Micro- and Nanosystems for Targeted Cancer Therapy.

Alginates have been widely explored due to their salient advantages of hydrophilicity, biocompatibility, mucoadhesive features, bioavailability, environmentally-benign properties, and cost-effectiveness. They are applied for designing micro- and nanosystems for controlled and targeted drug delivery and cancer therapy as alginate biopolymers find usage in encapsulating anticancer drugs to improve their bioavailability, sustained release, pharmacokinetics, and bio-clearance. Notably, these nanomaterials can be applied for photothermal, photodynamic, and chemodynamic therapy of cancers/tumors. Future explorations ought to be conducted to find novel alginate-based (nano)systems for targeted cancer therapy using advanced drug delivery techniques with benefits of non-invasiveness, patient compliance, and convenience of drug administration. Thus, some critical parameters such as mucosal permeability, stability in the gastrointestinal tract environment, and drug solubility ought to be considered. In addition, the comprehensive clinical translational studies along with the optimization of synthesis techniques still need to be addressed. Herein, we present an overview of the current state of knowledge and recent developments pertaining to the applications of alginate-based micro- and nanosystems for targeted cancer therapy based on controlled drug delivery, photothermal therapy, and chemodynamic/photodynamic therapy approaches, focusing on important challenges and future directions.

Effects of the Federal Aviation Administration's Compliance Program on aircraft incidents and accidents

• Restorative justice-based policies in aviation may be unsafe. • The FAA’s Compliance Program may reduce aviation safety. • Population-level data was evaluated using GLARMA modeling. • An increase in aircraft incidents and accidents resulted from the FAA’s Compliance Program. • A decrease in punishment may affect human behavioral responses. A novel enforcement policy based on restorative justice principles was implemented by the United States Federal Aviation Administration (FAA) in 2015. In this study, interrupted time series regression analyses using generalized linear autoregressive moving average (GLARMA) models were used to analyze FAA investigated incident and accident counts, runway incursion caused by pilot deviation, and National Transport Safety Board (NTSB) accident count data from June 2010 to September 2020. An association was observed between the change in FAA’s enforcement policy and the increase in aircraft incidents, accidents, and runway incursions post-intervention (2015–2020). These adverse safety outcomes appear to be directly related to this policy change. Results highlight the risk of moving away from punishment as a means of reinforcing safe behavior and the need for careful theory-based implementation of alternative approaches.

Features and Facts of a Gastroretentive Drug Delivery System-A Review.

English oral delivery of drug was the commonly used modality because of patient compliance and ease of administration. After oral administration of any drug, its bioavailability is affected by its residence time in stomach. Recently, gastroretentive drug delivery systems (GRDDS) have gained wide acceptance for drugs with a narrow absorption window, decreased stability at high alkaline pH, and increased solubility at low pH. This approach develops a drug delivery system, which gets retained within gastric fluid, thereby releasing its active principles in the stomach. Some methods used to achieve gastric retention of drugs include the use of effervescence agents, mucoadhesive polymers, magnetic material, bouncy enhancing excipient, and techniques that form plug-like devices that resist gastric emptying. This review provides a concise account of various attributes of recently developed approaches for GRDDS.

Antiplatelets Versus Anticoagulation in Cervical Artery Dissection: A Systematic Review and Meta-analysis of 2064 Patients.

Background and ObjectivesIn young people aged < 50 years, cervical artery dissection (CeAD) is among the most common causes of stroke. Currently, there is no consensus regarding the safest and most effective antithrombotic treatment for CeAD. We aimed to synthesize concrete evidence from studies that compared the efficacy and safety of antiplatelet (AP) versus anticoagulant (AC) therapies for CeAD.MethodsWe searched major electronic databases/search engines from inception till September 2021. Cohort studies and randomized controlled trials (RCTs) comparing anticoagulants with antiplatelets for CeAD were included. A meta-analysis was conducted using articles that were obtained and found to be relevant. Mean difference (MD) with 95% confidence interval (CI) was used for continuous data and odds ratio (OR) with 95% CI for dichotomous data.ResultsOur analysis included 15 studies involving 2064 patients, 909 (44%) of whom received antiplatelets and 1155 (56%) received anticoagulants. Our analysis showed a non-significant difference in terms of the 3-month mortality (OR 0.47, 95% CI 0.03–7.58), > 3-month mortality (OR 1.63, 95% CI 0.40–6.56), recurrent stroke (OR 0.97, 95% CI 0.46–2.02), recurrent transient ischaemic attack (TIA) (OR 0.93, 95% CI 0.44–1.98), symptomatic intracranial haemorrhage (sICH) (OR 0.38, 95% CI 0.12–1.19), and complete recanalization (OR 0.70, 95% CI 0.46–1.06). Regarding primary ischaemic stroke, the results favoured AC over AP among RCTs (OR 6.97, 95% CI 1.25–38.83).ConclusionOur study did not show a considerable difference between the two groups, as all outcomes showed non-significant differences between them, except for primary ischaemic stroke (RCTs) and complete recanalization (observational studies), which showed a significant favour of AC over AP. Even though primary ischaemic stroke is an important outcome, several crucial points that could affect these results should be paid attention to. These include the incomplete adjustment for the confounding effect of AP–AC doses, frequencies, administration compliance, and others. We recommend more well-designed studies to assess if unnecessary anticoagulation can be avoided in CeAD.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40268-022-00398-z.

Revenue Administration

This technical note describes CRM at a high level and how tax administrations can implement a CRM framework to significantly strengthen revenue outcomes. A tax administration’s primary role is to collect revenues on behalf of government to fund the country’s social and economic goals. Taxpayers are expected to comply with their tax obligations as stated in the law. Compliance is the degree to which taxpayers meet their obligations, whether voluntarily or through efforts by the tax administration to enforce compliance. Using CRM allows a country to optimize its revenue collection by identifying and focusing resources on the highest risks to the tax base. While the concepts of CRM are transferable to the customs context, this note focuses on tax administration compliance risks.

The Effect of Ownership The Effect of Tax Audit, Tax Amnesty and Non-Taxable Income on Income Tax Receipts at the Medan City Pratama Tax Service Office

This study aims to determine the effect of Tax Examination, Tax Amnesty and Non-Taxable Income on Income Tax Receipts at Medan City Tax Service Office. The population in this study is the taxpayer registered at the Medan City Tax Service Office. Samples taken from 20 taxpayer using accidental sampling method. The results showed that Tax Examination affected Income Tax Receipts. The results showed that Tax Amnesty affected Income Tax Receipts. The results showed that Non-Taxable Income affected Income Tax Receipts. F test results show that Tax Examination, Tax Amnesty and Non-Taxable Income affected Income Tax Receipts. The results of the coefficient of determination test show that the Income Tax Receipts variables can be explained by Tax Examination, Tax Amnesty and Non-Taxable Income while the remaining Income Tax Receipts variables can be explained by other variable not examined in this study such as Effectiveness of Tax Administration, Taxpayer Awareness, and Taxpayer Compliance.

P-66186255-114 - Peri-operative prescribing audit for cleft lip and palate inpatients at Royal Hospital for Children, Glasgow

<h3>Background</h3> Cleft lip and palate (CLP) surgery has been reported to result in significant postoperative pain, which can slow post-surgery feeding. Furthermore, postoperative wound infection is a recognized complication that may result in breakdown of the repair. The agreed peri-operative prescribing protocol designated by the National Cleft Surgical Service for Scotland, based at Royal Hospital for Children (RHC) Glasgow, includes peri-operative prescription of regular analgesia, antibiotic prophylaxis and IV fluids, titrated as per oral intake. <h3>Aim(s)/Objective(s)</h3> Review compliance of drug administration with RHC prescribing protocol. <h3>Methods</h3> Patient dataset obtained from logbook of theatre admission attendances to RHC for CLP surgical interventions in 2021. A sample of 30 patient electronic records that met the inclusion criteria were reviewed for prescription of regular analgesia (paracetamol and ibuprofen), antibiotic prophylaxis in line with the protocol and IV fluids as per oral intake. Standards set for 100% of patients to be prescribed analgesia, antibiotics and IV fluids as per the protocol. <h3>Results</h3> In the first cycle, all appropriate patients were prescribed oral antibiotics, 87% received post-operative IV antibiotics, 80% were prescribed regular paracetamol, 57% regular ibuprofen, and 83% received post-operative IV fluids. Posters describing the protocols were displayed in our operating theatres and surgical ward, and discussion of the protocol was introduced into the morning theatre brief. In the second cycle, 100% of patients received their oral and IV antibiotics and paracetamol, 93% received regular ibuprofen and 97% were prescribed post-operative IV fluids. <h3>Conclusions</h3> Improvements evident in compliance with prescribing protocol with education to the theatre and ward staff.

Mass drug administration for lymphatic filariasis elimination amidst COVID-19 pandemic in Odisha, India: A step towards achieving SDG-3.

Sustainable Development Goal-3 (SDG) aims to eliminate lymphatic filariasis by 2030 through >65% coverage and compliance of mass drug administration (MDA), the preventive chemotherapy strategy of delivering anthelminthic drugs. However, the ongoing COVID-19 pandemic has disrupted such programmes, yet MDA was administered during February 2021 in Odisha, India. We aimed to assess the coverage and compliance of the present round of MDA amidst the pandemic and explore factors for non-compliance in Cuttack district of Odisha, a filariasis endemic area. Community-based participants enrolled through multistage stratified sampling were administered a semi-structured questionnaire following COVID-19 protocols. The coverage of MDA was 93.2% whereas consumption was 73.7%. Participants reported that healthcare workers were motivated and satisfactorily explained the benefits of MDA but still fear of side-effects was the major cause of non-compliance. Nonetheless, this recent round of MDA was effective, despite challenges posed by the ongoing pandemic.

Epidemiology, Management, and Outcomes of Sepsis in ICUs among Countries of Differing National Wealth across Asia.

Rationale: Directly comparative data on sepsis epidemiology and sepsis bundle implementation in countries of differing national wealth remain sparse. Objectives: To evaluate across countries/regions of differing income status in Asia 1) the prevalence, causes, and outcomes of sepsis as a reason for ICU admission and 2) sepsis bundle (antibiotic administration, blood culture, and lactate measurement) compliance and its association with hospital mortality. Methods: A prospective point prevalence study was conducted among 386 adult ICUs from 22 Asian countries/regions. Adult ICU participants admitted for sepsis on four separate days (representing the seasons of 2019) were recruited. Measurements and Main Results: The overall prevalence of sepsis in ICUs was 22.4% (20.9%, 24.5%, and 21.3% in low-income countries/regions [LICs]/lower middle-income countries/regions [LMICs], upper middle-income countries/regions, and high-income countries/regions [HICs], respectively; P < 0.001). Patients were younger and had lower severity of illness in LICs/LMICs. Hospital mortality was 32.6% and marginally significantly higher in LICs/LMICs than HICs on multivariable generalized mixed model analysis (adjusted odds ratio, 1.84; 95% confidence interval, 1.00-3.37; P = 0.049). Sepsis bundle compliance was 21.5% at 1 hour (26.0%, 22.1%, and 16.2% in LICs/LMICs, upper middle-income countries/regions, and HICs, respectively; P < 0.001) and 36.6% at 3 hours (39.3%, 32.8%, and 38.5%, respectively; P = 0.001). Delaying antibiotic administration beyond 3 hours was the only element independently associated with increased mortality (adjusted odds ratio, 2.53; 95% confidence interval, 2.07-3.08; P < 0.001). Conclusions: Sepsis is a common cause of admission to Asian ICUs. Mortality remains high and is higher in LICs/LMICs after controlling for confounders. Sepsis bundle compliance remains low. Delaying antibiotic administration beyond 3 hours from diagnosis is associated with increased mortality. Clinical trial registered with www.ctri.nic.in (CTRI/2019/01/016898).

Knowledge Management and Low Operating Cost Indicator of Tax Administration Efficiency

The desire to reduce the operating cost of tax administration to achieve efficiency is obvious globally. However, knowledge management (KM) can reduce operating costs in tax administration to achieve efficiency. The objective of this study is to explain the various ways KM can reduce the cost of operation in tax administration. Qualitative data were sourced via a face-to-face interview with tax officers at Federal Inland Revenue Service (FIRS), Nigeria. Thus, qualitative data were sourced from 20 tax officers (participants) through a face-to-face interview. The data were sourced from tax officer II, tax officer I, the manager, the senior manager, the assistant director, and the deputy director. Participants (tax officers) were selected from domestic taxes, corporate development, modernisation, enforcement and compliance groups based on their experience. Also, data were sourced from national tax policy and a compendium of tax-related laws documents to support the interview data. Furthermore, semi-structured and open-ended interview questions were used as a guide for the face-to-face interview. The face-to-face interview was recorded with a smart voice recorder. Data were thematically analysed and administered with NVivo 10 qualitative software. In the process of analysis, sub-themes identified and reported based on the objective of the study and responses from participants were low manual operation, mistake, compliance and training cost. This study found that KM can reduce operating costs such as manual operation, mistakes, compliance and training costs in tax administration. Thus, KM can engender efficiency in tax administration through low manual operation, mistakes, compliance and training costs. The study recommends formal implementation of KM in tax administration in order to improve efficiency through low cost of administration.

Inequalities in Tobacco Retailer Compliance Violations Across the State of Oklahoma, 2015–2019

ObjectiveTo evaluate the relationship between compliance check violations, and characteristics of the tobacco retailer and neighborhood social vulnerability in Oklahoma.DesignThis cross-sectional study utilized the US Food and Drug Administration (FDA) Compliance Check Inspections of Tobacco Product Retailers database for 2015–2019. These data were combined with Neighborhood social vulnerability variables using the Centers for Disease Control and Prevention (CDC) Social Vulnerability Index.SettingThe setting of this study is the state of Oklahoma, USA.Outcome measuresThe outcome variable for this analysis was whether a sale was made to the youth during the compliance check (e.g., violation; yes/no) regardless of the outcome of the violation, and number of violations per a retailer.ResultsWe observed a strong association between having a violation and retailer store type, after controlling for socioeconomic vulnerability and percentage of mobile homes. The proportion of a tobacco retailer’s violations also varied by store type.ConclusionsMore targeted enforcements and retailer education by store type may be necessary to increase compliance.

Asthma management with combination of fluticasone and formoterol: the Indian perspectiverspective

Asthma is a major health problem globally that affects people across all the age groups. The prevalence of asthma is increasing worldwide, especially in the low- and middle-income countries. Asthma is controlled with inhaled corticosteroid (ICS) with as-needed or daily low-dose therapy. A step-up therapy to daily combination treatment with low- or medium-dose ICS/long-acting β-agonist (LABA) may be required for those with persistent symptoms. Asthma control levels are low despite the availability of many therapies. The efficacy of inhaled asthma therapy is dependent on the efficiency and reliability with which the drug is delivered to the lungs. Combination of an ICS and a LABA in a single inhaler is a safe, effective, and convenient treatment option for asthma management. Fluticasone and formoterol in combination ensure high potency action against anti-inflammation and rapid bronchodilation, and is a well-established ICS-LABA dual therapy. Rapid bronchodilator action of formoterol and fluticasone’s long-term action against inflammation are vital clinical attributes for optimal asthma maintenance treatment. Fluticasone/formoterol combination therapy is an efficacious and safe alternative treatment option for patients with moderate to severe asthma. The combination of the two in a single inhaler is beneficial with regards to ease of administration and patient compliance.

Chitosan-coated bovine serum albumin nanoparticles for topical tetrandrine delivery in glaucoma: in vitro and in vivo assessment

Glaucoma is one of the leading causes of blindness. Therapies available suffer from several drawbacks including low bioavailability, repeated administration and poor patient compliance with adverse effects thereafter. In this study, bovine serum albumin nanoparticles (BSA-NPs) coated with chitosan(CS) were developed for the topical delivery of tetrandrine (TET) for glaucoma management. Optimized nanoparticles were prepared by desolvation. pH, BSA, CS and cross-linking agent concentrations effects on BSA-NPs colloidal properties were investigated. CS-BSA-NPs with particle size 237.9 nm and zeta potential 24 mV was selected for further evaluation. EE% exceeded 95% with sustained release profile. In vitro mucoadhesion was evaluated based on changes in viscosity and zeta potential upon incubation with mucin. Ex vivo transcorneal permeation was significantly enhanced for CS coated formulation. In vitro cell culture studies on corneal stromal fibroblasts revealed NPs biocompatibility with enhanced cellular uptake and improved antioxidant and anti-proliferative properties for the CS-coated formulation. Moreover, BSA-NPs were nonirritant as shown by HET-CAM test. Also, bioavailability in rabbit aqueous humor showed 2-fold increase for CS-TET-BSA-NPs compared to TET with a sustained reduction in intraocular pressure in a rabbit glaucoma model. Overall, results suggest CS-BSA-NPs as a promising platform for topical ocular TET delivery in the management of glaucoma.

VACCINATION AGAINST HEPATITIS B IN ECUADOR: RISK GROUPS, COMORBIDITIES AND TOXIC HABITS IN NON-RESPONDING INDIVIDUALS.

Introduction; Hepatitis B virus is a viral agent that chronically infects humans, with an estimated 400 million people at permanent risk of developing cirrhosis and/or hepatocellular carcinoma. Immunization against hepatitis B (HB) is effective and safe, it is one of the most effective interventions for immunoprevention. However, there is a population group that does not respond to vaccination. Objective: to analyze the lack of response to anti-HB vaccine in the Ecuadorian population and its association with risk groups, comorbidities and toxic habits. Methods: A documentary design was applied through the analysis of different selected sources of scientific databases under inclusion and exclusion criteria, published in the last 10 years. The prevalence of HB shows endemicity in different regions. Health care providers are one of the groups with the highest risk of becoming infected, as well as newborns of seropositive mothers. The identified factors associated with the lack of response to vaccination are obesity, celiac disease, advanced age, immunocompetence, male sex, co-infections, smoking, drug addiction and alcoholism. Conclusion: Hepatitis B remains a major health problem throughout the world. Compliance of the complete administration of hepatitis B vaccine schedule is encouraged as established by health authorities in favor of children and people at risk, especially health personnel. Monitoring of antibodies and dose reinforcement is also advised.&#x0D; Keywords: hepatitis B, vaccines, occupational risks, immunization

Effects of Yi-Gan-san on the psychiatric behavior of children and adolescents with Tourette's Syndrome: A randomized, double-blind, controlled preliminary study

Ethnopharmacological relevanceGilles de la Tourette's Syndrome (TS) is a childhood-onset disease with clinical features of motor and phonic tics. Yi-Gan-san (YGS) is a traditional Chinese medicine formula that can reduce aggressiveness and agitation and inhibit dopamine function. This study investigated the effects of YGS on the psychiatric behavior of children and adolescents with TS. MethodsA double-blind, randomized, controlled preliminary study was conducted. A total of 38 patients with TS were assigned to the control group (CG, 19 patients) who received the oral administration of YGS placebo (90% starch and 10% YGS; 2.5 g thrice daily) or to a treatment group (TG, 19 patients) who received YGS for 4 weeks. The primary outcome measure was the change in Yale Global Tic Severity Scale (YGTSS) overall and subscale scores. ResultsThe intensity score for phonic tics before oral administration of YGS, and after 2 weeks, 3 weeks and 4 weeks was not significantly different between CG and TG groups (2.94 ± 1.14 vs 2.79 ± 1.08, p = .686; 2.29 ± 1.21 vs 1.95 ± 1.08, p = .370; 2.41 ± 1.18 vs 2.05 ± 1.51, p = .435; and 2.29 ± 1.26 vs 1.84 ± 1.42, p = .323, respectively), while the intensity score for phonic tics after 1-week oral administration of YGS in the TG was 1.89 ± 1.10 lower than 3.06 ± 1.39 in the CG (p = .008). ConclusionOral administration of YGS for 1 week only reduced the intensity of phonic tics compared with oral administration of YGS placebo, suggesting that YGS can reduce their intensity for a short period, and the compliance of oral administration of YGS for 4 weeks can be accepted in children and adolescents with Tourette's Syndrome. However, because this study was preliminary, the selection of an appropriate placebo and dosage and long-term observations are crucial areas for future studies.

An assessment of canine ectoparasiticide administration compliance in the USA

BackgroundThis study evaluated the timing of dog owner ectoparasiticide purchases to estimate administration compliance and assess the consequent impact of dose purchase gaps on the proportion of time that dogs were protected over a 12-month period.MethodsEctoparasiticide purchase transactions over a 12-month period were evaluated for 626 US veterinary hospitals to determine dose purchase timing and identify consequent gaps between dose administration in dogs. Orally administered prescription ectoparasitic medications with active ingredients from the isoxazoline family (afoxolaner, fluralaner, lotilaner, or sarolaner) were included in the analysis. A period was calculated for each of the four isoxazoline-containing medications that represented the duration of protection provided by two doses of ectoparasiticide plus the average gap between these two doses. The maximum percentage of time possible for ectoparasiticide protection for this aggregate period was then calculated for each active ingredient.ResultsEctoparasiticide transaction records of owners were analyzed for 506,637 dogs. These showed that 43% of dog owners purchased just one dose over the 12-month period considered. If a dog owner purchased more than one dose, then the timing of their transactions could create a time gap between the completion of ectoparasite protection from the first dose and onset of protection from the subsequent purchase and administration of the second dose. Such gaps were observed in purchases made by 31–65% of dog owners, depending on the selected active ingredient and number of doses. The average gap duration between dose purchases was calculated for all possible dose combinations over 12 months of ectoparasite protection. Time gaps between the first and second doses are as follows: for sarolaner, 20.3 weeks; for afoxolaner, 12.9 weeks; for fluralaner ,12.8 weeks; and for lotilaner, 8.9 weeks. The proportion of time when protection was provided during the aggregate period between administration of the first and second doses was as follows: for fluralaner, 65%; for lotilaner, 49%; for afoxolaner, 40%; and for sarolaner, 30%.ConclusionsDog owner ectoparasiticide purchase transactions showed that there were time gaps between doses leading to reduced ectoparasite protection. The longer re-administration interval for fluralaner, a consequence of its extended duration of activity, resulted in dog owners gaining the greatest proportion of ectoparasite protection time with this medication compared with shorter-acting monthly re-treatment medications.Graphical

Design of Oral Sustained-Release Pellets by Modeling and Simulation Approach to Improve Compliance for Repurposing Sobrerol.

Sobrerol, an oral mucolytic agent, in a recent study showed promise for treating multiple sclerosis. A human equivalent dose of 486 mg of sobrerol administered thrice daily (i.e., 1459 mg of daily dose) demonstrated the highest therapeutic efficacy for repurposing use, which also points out the poor compliance of administration. In this study, oral sustained-release pellets of sobrerol were successfully developed with evaluated manufacturing conditions and drug release kinetics. For design of the target drug product, we used a modeling and simulation approach to establish a predictive model of oral pharmacokinetic profile, by exploring the characteristics and correlations corresponding to the pharmacokinetics and pharmacodynamics of sobrerol, such as absorption lag time (0.18 h), time-scaling in vitro–in vivo correlation (tin-vitro = 0.494 tin-vivo − 0.0904), gastrointestinal transit time (8 h), minimum effective concentration (1.61 μg/mL), and duration of action (12.8 h). Results showed that the frequency of administration and the daily dose remarkably reduced by 33.3% (i.e., from thrice to twice daily) and 22.8%, respectively, which indicates that this prototype approach can be adopted for rapidly developing a modified-release dosage form of sobrerol, with improvement of compliance of administration and therapeutic efficacy.