Oral Administration Of Tablets Research Articles

Pharmacokinetics comparison of vardenafil as administered by an intranasal spray formulation vs a 10-mg oral tablet.

Oral vardenafil (VDF) tablet is an effective treatment for erectile dysfunction (ED), but intranasal administration with a suitable formulation can lead to a faster onset of action and offer more convenient planning for ED treatment. The primary purpose of the present pilot clinical study was to determine whether intranasal VDF with an alcohol-based formulation can result in more "user-friendly pharmacokinetics" as compared with oral tablet administration. This single-dose randomized crossover study was conducted in 12 healthy young volunteers receiving VDF as a 10-mg oral tablet or 3.38-mg intranasal spray. Multiple blood concentrations were obtained, and VDF concentrations were determined with a liquid chromatography-tandem mass spectrometry assay. Pharmacokinetic parameters following each treatment were compared and adverse events assessed. Pharmacokinetic parameters were obtained: apparent elimination rate constant, elimination half-life, peak concentration, peak time, total area under the curve, and relative bioavailability. Although mean apparent elimination rate constant, elimination half-life, peak concentration, and total area under the curve were similar between intranasal and oral administration, the median peak time from intranasal was much shorter (10vs 58minutes, P < .001, Mann-Whitney U test). The variability of the pharmacokinetic parameters was also less with intranasal than oral administration. The relative bioavailability of intranasal to oral was 1.67. Intranasal VDF caused transient but tolerable local nasal reactions in 50% of subjects. Other adverse events (eg, headache) were similar between the treatments. The incidence of adverse events was, however, significantly less in the second treatment after initial exposure to VDF. No serious adverse events were noted. Intranasal VDF potentially offers a more timely and lower dose for the treatment of ED in patients who can tolerate the transient local adverse reactions. The strength of this study is its randomized crossover design. Because the study was conducted in 12 healthy young subjects, the results may not reflect those observed in elderly patients who may be likely taking VDF for ED. Nevertheless, the changes of pharmacokinetic parameters in the present study are likely a reflection of the differences between intranasal and oral administration of the formulations. Our study indicated that the present VDF formulation, when administered intranasally, can achieve a more rapid but similar plasma concentration with only about one-third dose when compared with the oral administration.

TOXICOLOGICAL CHARACTERISTICS OF TABLETS WITH AN EXTRACT OF POTENTILLA ALBA L. WITH REPEATED ADMINISTRATION TO RABBITS

Relevance. In recent years, there has been increased interest in medicinal plants, in particular, Potentilla alba L., used for the treatment of endocrine diseases, on the basis of which the thyroid drug - tablets for oral administration, containing 0,150 g of dry extract of roots and rhizomes of this plant. The dry extract of rhizomes and roots of Potentilla alba L. normalizes the functional activity of the thyroid gland, has an immunomodulatory and hypoli-pidemic effect in the rat model of experimental hypothyroidism. Aim. A study of the toxicity of tablets with dry extract of Potentilla alba L. with repeated administration to justify the conduct of clinical trials. Material and methods. The study of general toxic effects of tablets was carried out on 15 clinically healthy male rabbits of Soviet Chinchilla breed, which were given tablets in doses of 37,5 and 75 mg/kg for 90 days. Control animals received placebo tablets. Integral, hematological and biochemical parameters were recorded, electrocardiograms (ECG) were taken, and pathohistological studies were performed to detect health abnormalities. Results. Administration of tablets at 9- and 17-fold therapeutic doses had no effect on basic hematological, biochemical and ECG parameters charac-terizing functional state of liver, kidneys, cardiovascular system of experimental animals. Administration of tablets to rabbits in the tested doses caused a moderate dose-dependent decrease in their body weight gain, possibly related to the hypolipidemic effect. Pathohistological examination re-vealed changes that were dose-dependent: full-bloodedness of internal organs, including pituitary gland; stimulation of hematopoietic function charac-terized by increased spleen follicles and their confluence; inhibition of thyroid function and partially of spermatogenesis. At the maximum tested dose of 75 mg/kg, the studied drug had a selective specific pharmacological effect on the pituitary gland, causing a decrease in the size of basophilic cells. No irritating effect of the tablets on the mucosa of the gastrointestinal tract of animals was noted. Conclusion. The obtained results of the preclinical toxicological examination of tablets 0.150 g were included in the dossier on the drug prepared for transfer to the Ministry of Health of the Russian Federation for obtaining permission to conduct clinical trials.

Ospemifene (Osphena)

&#x0D; CADTH reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class.&#x0D; The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada's federal, provincial, and territorial governments, with the exception of Quebec.&#x0D; This review assesses Ospemifene (Osphena), 60 mg tablets for oral administration.&#x0D; Indication: Indicated in post-menopausal women for the treatment of moderate to severe dyspareunia and/or vaginal dryness, symptoms of vulvar and vaginal atrophy, a component of genitourinary syndrome of menopause.&#x0D;

Hyperthermia-Induced In Situ Drug Amorphization by Superparamagnetic Nanoparticles in Oral Dosage Forms.

Superparamagnetic iron oxide nanoparticles (SPIONs) generate heat upon exposure to an alternating magnetic field (AMF), which has been studied for hyperthermia treatment and triggered drug release. This study introduces a novel application of magnetic hyperthermia to induce amorphization of a poorly aqueous soluble drug, celecoxib, in situ in tablets for oral administration. Poor aqueous solubility of many drug candidates is a major hurdle in oral drug development. A novel approach to overcome this challenge is in situ amorphization of crystalline drugs. This method facilitates amorphization by molecular dispersion of the drug in a polymeric network inside a tablet, circumventing the physical instability encountered during the manufacturing and storage of conventional amorphous solid dispersions. However, the current shortcomings of this approach include low drug loading, toxicity of excipients, and drug degradation. Here, doped SPIONs produced by flame spray pyrolysis are compacted with polyvinylpyrrolidone and celecoxib and exposed to an AMF in solid state. A design of experiments approach was used to investigate the effects of SPION composition (Zn0.5Fe2.5O4 and Mn0.5Fe2.5O4), doped SPION content (10–20 wt %), drug load (30–50 wt %), and duration of AMF (3–15 min) on the degree of drug amorphization. The degree of amorphization is strongly linked to the maximum tablet temperature achieved during the AMF exposure (r = 0.96), which depends on the SPION composition and content in the tablets. Complete amorphization is achieved with 20 wt % Mn0.5Fe2.5O4 and 30 wt % celecoxib in the tablets that reached the maximum temperature of 165.2 °C after 15 min of AMF exposure. Furthermore, manganese ferrite exhibits no toxicity in human intestinal Caco-2 cell lines. The resulting maximum solubility of in situ amorphized celecoxib is 5 times higher than that of crystalline celecoxib in biorelevant intestinal fluid. This demonstrates the promising capability of SPIONs as enabling excipients to magnetically induce amorphization in situ in oral dosage forms.

THE USE OF ARABINOGALACTAN IN THE DEVELOPMENT OF TABLETS WITH DIHYDROQUERCETIN

Abstract. The possibility of using arabinogalactan in the preparation of oral tablets based on the natural bioflavonoid dihydroquercetin has been shown. The composition and technology of tablets using the wet granulation method has been developed. The quantitative content of dihydroquercetin in tablets was determined by HPLC. Aim. Development the composition and technology of dihydroquercetin tablets for oral administration using arabinogalactan.

Pharmacokinetics and Effects on Saliva Flow of Sublingual and Oral Atropine in Clozapine-Treated and Healthy Adults: An Interventional Cross-Over Study.

Sublingual atropine is an effective treatment of clozapine-induced hypersalivation. This study aims to investigate the pharmacokinetics of atropine after sublingual and oral administration and study the dose effect of atropine on saliva secretion. An interventional cross-over clinical trial where participants received 0.6 mg and 1.2 mg atropine sulfate sublingual solution and 0.6 mg oral tablet. Atropine plasma concentration was measured over 9 hours with validated LC-MS/MS method. Atropine effects on saliva secretion rate, visual acuity and accommodation, and vital signs were assessed. Four clozapine-treated and three healthy participants were enrolled in the study. The area under the atropine plasma concentration-time curve (AUC0-∞) was highest after the 1.2 mg sublingual solution administration in comparison with 0.6 mg tablet or sublingual solution (8.58±1.66 µg.L-1.h vs. 4.65±1.29 vs. 2.98±0.73 µg.L-1.h, respectively). The Cmax for the 0.6 mg and 1.2 mg sublingual solutions was 1.11±0.99 and 1.76±0.62 µg.L-1, and tmax was 2.18±0.59 and 1.9±0.71 h, respectively. In comparison with the 0.6 mg sublingual solution dose, the saliva secretion reduction was larger after the oral tablet administration (-40% (-59, -22%) vs. -69% (-80, -57)) and largest after the 1.2 mg sublingual solution administration (-79% (-93,-64)). Both the sublingual and oral atropine are effective in reducing the saliva secretion however at a lower plasma concentration after sublingual administration, with a dose-dependent effect. Both have significantly reduced the blood pressure and pulse rate over 3 hours without significant changes in vision. No major safety concerns were reported.

Совершенствование методов хирургического лечения патологии шейки матки

Aim: to improve outcomes of the surgical management of cervix disorders by using a hemostatic agent with antimicrobial activity. Patients and Methods: the study included 47 women, 25–45 years of age, with CIN II/III to whom cervical radiofrequency ablation was performed. The main group comprised 26 (55.3%) patients. During the ablation procedure, a 1% aqueous solution of incomplete polyacrylic acid silver salt with integrated nanoparticles was used as an additional treatment for this group of patients. The control group consisted of 21 (44.7%) patients for whom the standard ablation technique was used. The assessed criteria included the clinical course and laboratory test results before and three months after the surgical treatment, as well as the bleeding rates. Results: in the main group of patients, the mean leucocyte number in the smear after the treatment was 9.2±1.2 per field of vision, in the control group — 18.5±2.9; pH of the vaginal discharge — 4.2±0.2 (from 3.8 to 4.5) and 4.7±0.2 (from 4.2 to 5.8), respectively. Intraoperative bleeding from the surgical wound which required additional manipulations was reported in 2 (7.7%) patients of the main group and 2 (9.5%) patients of the control group. Ten days after the surgery, one patient (3.8%) from the main group had complaints on heavy bloody vaginal discharge. Three (14,3%) patients from the control group had the same complaint 11–13 days after the surgery (3.7 relative risk, 95% confidence interval (CI) 1,0–18,2) which required the use of tranexamic acid as tablets for oral administration. Three months after the surgery the clue cells were found in one (3.8%) patient of the main group and in 7 (33.3%) patients of the control group (8.7 relative risk, 95% CI 1.2–16.5), and the fungal mycelia — only in 8 (38.1%) patients of the control group. Conclusion: the use of a 1% aqueous solution of incomplete polyacrylic acid silver salt with integrated nanoparticles during the cervical ablation resulted in a statistically significant reduction of the bleeding risk and improved the vaginal microflora profile in postoperative period. KEYWORDS: cervical dysplasia, cervical excision, cervical conization, bacterial vaginosis, hemostatic agent, bleeding. FOR CITATION: Il’ina I.Yu., Dobrokhotova Yu.E. Optimizing surgical management of uterine cervix disorders. Russian Journal of Woman and Child Health. 2022;5(3):188–193 (in Russ.). DOI: 10.32364/2618-8430-2022-5-3-188-193.

Clinical Pharmacokinetics of the Androgen Receptor Inhibitor Darolutamide in Healthy Subjects and Patients with Hepatic or Renal Impairment.

BackgroundDarolutamide is a second-generation androgen receptor inhibitor approved for the treatment of nonmetastatic castration-resistant prostate cancer at a dosage of 600 mg orally twice daily.ObjectiveWe aimed to fully characterize the pharmacokinetic profile of darolutamide, its diastereomers, and its main active metabolite, keto-darolutamide.MethodsSingle-dose and multiple-dose pharmacokinetics of 14C-labeled and non-labeled darolutamide were evaluated in healthy subjects and patients with hepatic or renal impairment.ResultsFollowing darolutamide oral tablet administration, peak plasma concentrations were reached 4–6 h after dosing. Darolutamide elimination was characterized by a half-life of 13 h. Steady state was reached after approximately 2 days of twice-daily dosing. Pharmacokinetics of the diastereomers and keto-darolutamide followed similar trends to the parent compound. Darolutamide absorption from the tablet was lower than from the oral solution; tablet absolute bioavailability was ~30% in the fasted state but improved to 60–75% when given with food. The unbound fraction of darolutamide in plasma was 7.8%. The administered 1:1 ratio of the diastereomers (S,R)-darolutamide and (S,S)-darolutamide changed to ~1:6 in plasma following multiple dosing. Similar exposure and diastereomer ratios after single and multiple dosing indicate time-independent (no autoinduction) linear pharmacokinetics. Darolutamide exposure increased in patients with moderate hepatic or severe renal impairment vs healthy subjects; dose adaptation at treatment initiation should be considered in these patients.ConclusionsDarolutamide 600 mg twice daily demonstrates predictable linear pharmacokinetics and sustainably high plasma concentrations, suggesting the potential for constant inhibition of the androgen receptor signaling pathway.Clinical Trials RegistrationNCT02418650, NCT02894385, NCT02671097.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40262-021-01078-y.

FORMULATION OPTIMIZATION AND CHARACTERIZATION OF AQUEOUS INJECTION CONTAINING POORLY SOLUBLE DRUG USING MIXED HYDROTROPIC SOLUBILIZATION

Objective: Mefenamic acid (MFA) is an NSAID that exhibits anti-inflammatory analgesic and antipyretic activity. Peak plasma levels are attained in 2-4 h and the elimination half-life approximates 2 h, repetitive administration of tablets for 3-5 times a day is desired. It is supplied only in the form of tablets for oral administration. In acute conditions drug administered parenterally could give rapid relief from severe symptoms like pain. Thus, formulation of injectable formulation of MFA could be better alternative compared to conventional tablet dosage form. The low aqueous solubility of MFA precludes its use in parenteral formulation development.&#x0D; Methods: In this work attempt were made to enhance the aqueous solubility of mefenamic acid using mixed solvency technique. For that different hydrotropic agents such as Urea, Sodium acetate, sodium benzoate, sodium citrate and their blends were evaluated. Optimal concentration of hydrotropic agent in blend was determined using D-optimal mixture experimental design. The optimized bled was used to develop the aqueous injection of mefenamic acid. The developed injection was subjected for various quality control tests and stability of developed formulation was also evaluated.&#x0D; Results: The aqueous solubility in optimized blend of hydrotropic agent batches (U: SA: SB: SC, 4:4:23:9 %w/v) showed 835.71-fold compared to MFA solubility in distilled water. The quality control tests for parenteral formulation and accelerated stability study were found to be within prescribed limits and stable.&#x0D; Conclusion: The inadequate solubility of MFA was overcome, and aqueous injection was successfully developed which can be serve as cost effective treatment in various indications.

Oral pharmacokinetic profile of fipronil and efficacy against flea and tick in dogs.

Fipronil (FIP) is an ectoparasiticide of the phenylpyrazole class, used in veterinary medicine in topical form. Supported by evidence of uncontrolled human exposure to FIP and environmental damage caused by commercially available formulations, its use by oral administration has become promising. The effectiveness of FIP against the flea Ctenocephalides felis felis and the tick Rhipicephalus sanguineus and its pharmacokinetics and main active metabolite, fipronil sulfone (SULF) were evaluated after single oral administration of tablets in three different doses (2, 4, and 6mg/kg) in dogs. Through the plasma concentration curves, it was possible to observe that the FIP showed rapid absorption and metabolization and slow elimination. The values of Cmax (β=0.7653) and AUC0- t (β=0.3209) did not increase proportionally with increasing dose. At 48h after treatment, doses of 4mg/kg (AUC0- t =442.39±137.35µg/ml*h) and 6mg/kg (AUC0- t =421.32±102.84µg/ml*h) provided 100% and 99% efficacy against fleas, and 95% and 98% against ticks, respectively. The estimated EC90 of FIP +SULF was 1.30µg/ml against C. felis felis and 2.16µg/ml against R. sanguineus. The correlation between the FIP pharmacokinetic and efficacy data demonstrated its potential for oral administration in the form of tablets for the control of ectoparasites in dogs, as a safer alternative for animals, humans, and the environment, aligned with the One Health concept.

Physiologically based pharmacokinetic modelling of treprostinil after intravenous injection and extended-release oral tablet administration in healthy volunteers: An extrapolation to other patient populations including patients with hepatic impairment.

AimsPulmonary arterial hypertension (PAH) is characterized by increased pulmonary arterial pressure, resulting in right ventricular overload, right heart failure and eventually death. Treprostinil is a prostacyclin analogue that is used in the treatment of PAH. As an orphan drug, limited information is available regarding its disposition and its use in special populations such as elderly, paediatric and pregnant patients. The objective of the current study was to develop a robust physiologically based pharmacokinetic (PBPK) model for treprostinil intravenous injection and extended‐release tablet as the first step to optimize treprostinil pharmacotherapy in patients.MethodsPBPK model was built using Simcyp simulator which integrated physicochemical properties, observed or predicted parameters for drug absorption, distribution and elimination for treprostinil, and population specific physiological characteristics. Three clinical trials after intravenous infusion and nine studies after oral administration of treprostinil extended‐release tablet in healthy volunteers were used to develop and validate the model. The simulated PK profiles were compared with the observed data. Extrapolation of the model to patient populations including patients with hepatic impairment was conducted to validate the predictions.ResultsMost of the observed data were within the 5th and 95th percentile interval of the prediction. Most of the percentage error in the PK parameters were within ±50% of the corresponding observed parameters. The developed model predicted the lung exposure of treprostinil to be approximately 0.17 times of concentration in plasma.ConclusionPredicted absorption, distribution, and metabolic enzyme kinetics gave an insight into the disposition of treprostinil in humans. Extrapolation of the established model to patient populations with hepatic impairment successfully documented the model reliability. The developed model has the potential to be used in the PK predictions in other special patient populations with different demographic, physiological and pathological characteristics.

Non‐Invasive Sweat‐Based Tracking of L‐Dopa Pharmacokinetic Profiles Following an Oral Tablet Administration

AbstractLevodopa (L‐Dopa) is the “gold‐standard” medication for symptomatic therapy of Parkinson disease (PD). However, L‐Dopa long‐term use is associated with the development of motor and non‐motor complications, primarily due to its fluctuating plasma levels in combination with the disease progression. Herein, we present the first example of individualized therapeutic drug monitoring for subjects upon intake of standard L‐Dopa oral pill, centered on dynamic tracking of the drug concentration in naturally secreted fingertip sweat. The touch‐based non‐invasive detection method relies on instantaneous collection of fingertip sweat on a highly permeable hydrogel that transports the sweat to a biocatalytic tyrosinase‐modified electrode, where sweat L‐Dopa is measured by reduction of the dopaquinone enzymatic product. Personalized dose‐response relationship is demonstrated within a group of human subjects, along with close pharmacokinetic correlation between the finger touch‐based fingertip sweat and capillary blood samples.

Non-Invasive Sweat-Based Tracking of L-Dopa Pharmacokinetic Profiles Following an Oral Tablet Administration.

Levodopa (L-Dopa) is the "gold-standard" medication for symptomatic therapy of Parkinson disease (PD). However, L-Dopa long-term use is associated with the development of motor and non-motor complications, primarily due to its fluctuating plasma levels in combination with the disease progression. Herein, we present the first example of individualized therapeutic drug monitoring for subjects upon intake of standard L-Dopa oral pill, centered on dynamic tracking of the drug concentration in naturally secreted fingertip sweat. The touch-based non-invasive detection method relies on instantaneous collection of fingertip sweat on a highly permeable hydrogel that transports the sweat to a biocatalytic tyrosinase-modified electrode, where sweat L-Dopa is measured by reduction of the dopaquinone enzymatic product. Personalized dose-response relationship is demonstrated within a group of human subjects, along with close pharmacokinetic correlation between the finger touch-based fingertip sweat and capillary blood samples.

Formulation, Design and In-Vitro Characterization of Clopidogrel Bisulphate Nanosponge Tablets for Oral Administration

Poor bioavailability by the oral route is noticeable with the majority of new active pharmaceutical ingredients due to its dissolution rate limited absorption. A second-generation thienopyridine antiplatelet drug, though, it is BCS class II drug results in poor oral bioavailability. The present investigation was undertaken to prepare polymeric nanosponges to achieve improved solubility of clopidogrel bisulphate. Nanosponges using ethyl cellulose as a polymer and glutarldehyde as a cross-linker were prepared successfully by emulsion solvent diffusion method. Drug polymer compatibility study were performed by FTIR and DSC. To obtain optimized batch, 32 factorial designs were performed and all batches were evaluated. C1-C9 batches yields particle size (nm) between 87.28-183(nm), % drug content between 71.073±1.066 -88.663 ±0.549, % entrapment efficiency between 51.719±0.775- 81.765±0.506, % drug release 75.120±0.407-97.416±0.336. Optimized batch exhibited particle size 87.28nm, % drug content 88.663 ±0.549, % entrapment efficiency 81.765±0.506, % drug release 97.416±0.336. An SEM and TEM image of optimized batch shows spongy and spherical nature of nanosponges. The optimized nanosponge formulations were converted into tablets to achieve immediate release drug delivery for oral route. These tablets were prepared using crospovidone and pregelatinised starch. All nine tablet batches were evaluated and F3 batch shows good results i.e. hardness (kg/cm2) 3.71±0.04, in- vitro disintegration time (min) 3.21±0.025 and % drug release 99.18±1.38. In vitro dissolution studies indicate that percent cumulative drug release follows zero order kinetics. Accelerated and long term stability data revealed no significant change in drug content and drug release at the end of 6 months. In conclusion, nanosponges could be a newly emerging approach to enhance aqueous solubility of BCS Class II drugs.

A randomized, controlled field study to assess the efficacy and safety of lotilaner flavored chewable tablets (Credelio\u2122 CAT) in eliminating fleas in client-owned cats in the USA

BackgroundStudies show that the novel isoxazoline, lotilaner (Credelio™ CAT; Elanco Animal Health), which is administered orally to cats, provides rapid and sustained flea kill for least 1 month following administration with a wide safety margin. A clinical trial was undertaken to confirm its efficacy, impact on flea allergy dermatitis (FAD) and safety under field conditions.MethodsA total of 343 cats were enrolled in the study at 11 veterinary clinics in the USA. Upon inclusion, cat households were randomized at a ratio of 2:1 to receive lotilaner tablets at the recommended dose (minimum 6 mg/kg) or a topical formulation containing fipronil + S-methoprene (Frontline® Plus for cats; Boehringer Ingelheim), administered per label. Owners were dispensed treatments for administration on days 0, 30 and 60; all household cats were administered the same treatment. Flea counts were made on primary cats (1 cat per household) on days 0 (pre-treatment), 30, 60 and 90. Flea allergy dermatitis was assessed on days 30, 60 and 90 for all cats with signs of FAD on day 0. Lotilaner-treated cats were also assessed for their acceptance of oral tablet administration by the pet owner, and safety was assessed for all cats in both groups.ResultsLotilaner efficacy was 98.3, 99.9 and 99.9% on days 30, 60 and 90, respectively, while the efficacy of fipronil + S-methoprene was 61.6, 75.4 and 84.7%, respectively (P < 0.0001, within both groups and all days). Flea counts were significantly lower in the lotilaner group than in the fipronil + S-methoprene group (P < 0.0001) on each assessment day. On day 90, 98.3% of lotilaner-treated cats and 28.8% of fipronil + S-methoprene-treated cats were free of fleas. Owners successfully administered 99.5% of tablets to their cats. Total FAD score was reduced significantly following treatment in both groups by day 30 (lotilaner: P < 0.0001; fipronil + S-methoprene: P = 0.0041) and continued to decrease following multiple treatments. Total FAD scores were also significantly lower in the lotilaner group than in the fipronil + S-methoprene group on day 90 (P = 0.0006 for FAD total score). Pruritus scores were significantly lower in the lotilaner group on all assessment days.ConclusionA single lotilaner treatment, administered by the pet owner, was > 98% efficacious in reducing flea counts within 30 days. Three consecutive monthly lotilaner treatments resulted in nearly 100% reduction in flea infestation. In the evaluations of flea counts, number of cats free from fleas and pruritus FAD score, lotilaner was shown to be superior to fipronil + S-methoprene at all time points. Lotilaner was more efficacious than fipronil + S-methoprene and was associated with greater reduction in FAD signs. Lotilaner flavored tablets were well accepted by cats. Adverse reactions were mild and infrequent, confirming the safety of lotilaner tablets in client-owned cats.Graphical

The study of permanent problems of pharmacist's protocol realization concerning wet cough

Cough is a typical symptom of common cold and a frequent reason for visiting the pharmacies and purchasing over-the-counter (OTC) medicines. Dispensing drugs for the symptomatic relief of cough is carried out in accordance with the current pharmacist’s protocol, which describes the algorithm of pharmaceutical care.&#x0D; Aim of the study – to determine the permanent problems of pharmacist’s protocol realization concerning wet cough by questionnaire survey of pharmacy workers.&#x0D; The study was carried out by 2 steps: step 1 – in 2015 (May–December), step 2 – in 2020 (January–October). One developed questionnaire was used for both steps of the research process. 168 of pharmacy employees took part in step 1, and 144 – in step 2. Methods: systemic approach, questionnaire survey, analytical, statistical and comparative.&#x0D; It was found that 75,6% of pharmaceutical workers in 2015 and 97,2% in 2020 (p &lt; 0,05) asked pharmacy customers about «threatening» symptoms in patients with cough. If any «threatening» symptom was identified, 73,2% of respondents in 2015 compared with 96,4% in 2020 referred patients to a doctor (p &lt; 0,05), 18,9% vs 29,3% of respondents recommended and dispensed antibiotics (p &lt; 0,05), 13,4% vs 19,3% – antiviral drugs (p &gt; 0,05), 18,1% vs 65,7% – analgesics-antipyretics/non-steroidal anti-inflammatory drugs (p &lt; 0,05), 3,1% vs 37,1% – vitamin and mineral complexes (p &lt; 0,05).&#x0D; Acetylcysteine (76,2% of respondents in 2015 vs 89,6% in 2020, p &lt; 0,05) and ambroxol (59,5% of respondents in 2015 vs 84,7% in 2020, p &lt; 0,05) were the most frequently recommended and dispensed medicines from pharmacies for symptomatic pharmacotherapy of wet cough. At the same time, 11,3% of respondents in 2015 vs 8.3% in 2020 (p &gt; 0.05) still dispensed antitussive drugs which are contraindicated in this case.&#x0D; In 2015 priority was given to syrups (85,1%) and tablets for oral administration (62,5%), but in 2020 – sachets (80,6%) and tablets for oral administration (79,9%). However, 8,3% of pharmacy workers in 2015 vs 15,2% in 2020 never interviewed pharmacy customers regarding co-morbidity in patients (p &gt; 0.05).&#x0D; Quality and safety of drugs were the most important motivating factors in OTC-drugs choice at both steps of the study. In 2020 their influence on the choice of OTC-drugs increased significantly (p &lt; 0.05).&#x0D; According to the results of the questionnaire survey, 5 main permanent problems associated with the pharmacist’s protocol realization concerning wet cough have been identified, the solution of which will improve the quality of pharmaceutical care in pharmacies.

Effect of food on the pharmacokinetics of oral cefuroxime axetil in dogs

Cefuroxime axetil pharmacokinetic profile was investigated in 12 Beagle dogs after single intravenous and oral administration of tablets or suspension at a dose of 20mg/kg, under both fasting and fed conditions. A three-period, three-treatment crossover study (IV, PO under fasting and fed condition) was applied. Blood samples were withdrawn at predetermined times over a 12-hr period. Cefuroxime plasma concentrations were determined by HPLC. Data were analyzed by compartmental analysis. No statistically significant differences were observed between formulations and feeding conditions on PK parameters. Independently of the feeding condition, absorption of cefuroxime axetil after tablet administration was low and erratic. The drug has been quantified in plasma in 3 out of 6 and 5 out of 6 dogs in the fasted and fed groups. For this formulation, the bioavailability (F), peak plasma concentration (Cmax ), and area under the concentration-time curve (AUC) of cefuroxime axetil were significantly enhanced (p<.05) by the concomitant ingestion of food (32.97±13.47-14.08±7.79%, 6.30±2.62-2.74±0.66µg/ml, and 15.75±3.98-7.82±2.76µg.hr/ml for F, Cmax, and AUC in fed and fasted dogs, respectively), while for cefuroxime axetil suspension, feeding conditions affected only the rate of absorption, as reflected by the significantly shorter absorption half-life (T½(a) ) and time to peak concentration (Tmax ) (0.55±0.27-1.15±0.19hr and 1.21±0.22-1.70±0.30 for T½(a) and Tmax in fed and fasted dogs, respectively). For cefuroxime axetil tablets, T>MIC (≤1µg/ml) was <2hr in fasted and ≈4hr in fed animals, and for cefuroxime axetil suspension, T>MIC (≤1µg/ml) was ≈5hr and for T >MIC (≤4µg/ml) was ≈2.5hr for fasted and fed dogs, respectively. Cefuroxime axetil as a suspension formulation seems to be a better option than tablets. However, its short permanence in plasma could reduce its clinical usefulness in dogs.

A Suspension Method Using a Planetary Centrifugal Mixer for Oral Administration of Tablets or Capsules by a Feeding Tube

A Suspension Method Using a Planetary Centrifugal Mixer for Oral Administration of Tablets or Capsules by a Feeding Tube

Intranasal dolutegravir sodium loaded nanoparticles of hydroxypropyl-beta-cyclodextrin for brain delivery in Neuro-AIDS

Dolutegravir sodium (DTG) loaded nanoparticles (NPs) were prepared by cross-linking Hydroxypropyl-β-cyclodextrin (HPβCD) with diphenyl carbonate to enhance its CNS uptake via intranasal delivery. NPs were characterized for various parameters like size, drug loading, in vitro release, safety and CNS uptake and optimized using quadratic response surface methodology (RSM) employing 2-factor, 5-level circumscribed central composite design. The batch of NPs containing DTG:HPβCD; 1:4.16 was considered optimum as uniform small NPs (size; 81±3 nm, PDI 0.378 ± 0.04) with high drug loading (14.9 ± 1.4%) and entrapment efficiency (77 ± 3.35%). NPs produced sustained drug release (89.51 ± 0.56% in 6 h) by Fickian diffusion mechanism, they provided 2.54 folds greater permeability of DTG compared to free drug and were non-toxic to L929 cell line. Significantly higher concentration of DTG in the CSF (24.89±4.56μg/mL) and higher CSF:Plasma ratio(1.64) was achieved from intranasal NPs as compared to the reported DTG concentration in the CSF (18 ng/mL) and CSF:Plasma ratio (0.11–0.66) following oral administration of tablet. High brain drug transport percentage (83.47%) from intranasal NPs confirms nose to brain transport of the drug. Gamma scintigraphy studies in rats revealed enhanced CNS uptake of drug from NPs. These results suggest that the present investigation hold promise for management of Neuro-AIDS.

Pharmacokinetic (PK) Assessment of Perampanel Intravenous (IV) Formulation as a Bioequivalent Alternative to Oral Tablet Administration (P1.5-029)

Pharmacokinetic (PK) Assessment of Perampanel Intravenous (IV) Formulation as a Bioequivalent Alternative to Oral Tablet Administration (P1.5-029)