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Topical corticosteroids are often utilized as the first-line treatment for vulvar lichen sclerosus (VLS). However, there is wide variability in dosing regimens, as well as a lack of consensus on maintenance dosing. Available guidelines on dosing frequency and regimen continuation for VLS are based on clinical expert opinion and do not necessarily reflect the pharmacokinetics of topical corticosteroids. Over the past few decades, there have been many advances in the techniques used to measure the local and systemic absorption of topical corticosteroids. These techniques have led to a greater understanding of the pharmacokinetics and bioavailabilities of these medications. However, it is not clear how this new information has been applied in evaluating dosing regimens and commonly cited risks when considering short- and long-term use in different vulvar dermatoses. This purpose of this review is to evaluate the available evidence on pharmacokinetics, absorption rates, and concentration levels of topical corticosteroids in lesional and nonlesional skin. Additionally, the evidence regarding commonly cited risks of topical corticosteroid use, including dermal thinning, adrenal suppression, systemic immunosuppression, and tachyphylaxis are reviewed. Differences in the effects of topical corticosteroids on the varied tissues of the vulva are specifically explored. Finally, these considerations are applied to evaluate the current treatment guidelines for VLS to provide direction in determining an evidenced-based dosing regimen and to inform future research in this area. Mautz TT, Krapf JM, Goldstein AT. Topical Corticosteroids in the Treatment of Vulvar Lichen Sclerosus: A Review of Pharmacokinetics and Recommended Dosing Frequencies. Sex Med Rev 2021;XX:XXX-XXX.

Millions of people die each year from viral infections across the globe. There is an urgent need to overcome the existing gap and pitfalls of the current antiviral therapy which include increased dose and dosing frequency, bioavailability challenges, non-specificity, incidences of resistance and so on. These stumbling blocks could be effectively managed by the advent of nanomedicine. Current review emphasizes over an enhanced understanding of how different lipid, polymer and elemental based nanoformulations could be potentially and precisely used to bridle the said drawbacks in antiviral therapy. The dawn of nanotechnology meeting vaccine delivery, role of RNAi therapeutics in antiviral treatment regimen, various regulatory concerns towards clinical translation of nanomedicine along with current trends and implications including unexplored research avenues for advancing the current drug delivery have been discussed in detail.

The first-generation taxanes (including paclitaxel and docetaxel) are widely used for the treatment of various cancers in clinical settings. In the past decade, a series of new-generation taxanes have been developed which are effective in the inhibition of tumor resistance. However, intravenous (i.v.) infusion is still the only route of administration, and may result in serious adverse reactions with respect to the utilization of Cremophor EL or Tween-80 as solvent. Besides, the dosing schedule is also limited. Therefore, oral administration of taxanes is urgently needed to avoid the adverse reactionss and increase dosing frequency. In this review, we first outlined the discovery and development of taxane-based anticancer agents. Furthermore, we summarized the research progress on the oral formulations of taxanes and proposed some thoughts on the future development of oral taxane formulations.

Although buprenorphine is the most frequently used opioid analgesic in common marmosets (Callithrix jacchus), there is limited information in the literature supporting current dosing regimens used for this species. The purpose of this study was to determine the pharmacokinetic profiles of single-dose buprenorphine HCl administered intramuscularly (IM) at 0.01 mg/kg in 6 adult marmosets (1.8 to 12.8 y old; 2 males, 4 females) and subcutaneously (SQ) at 0.01 mg/kg in 6 adult marmo- sets (2.3-4.4 y old; 3 males, 3 females) by mass spectrometry. Blood was collected at multiple time points from 0.25 to 24 h from unsedated animals following a hybrid sparse-serial sampling design. The maximal observed plasma concentration of buprenorphine (Cmax) administered IM (2.57 ± 0.95 ng/mL) was significantly higher than administered SQ (1.47 ± 0.61 ng/mL). However, the time to Cmax(Tmax) was not statistically different between routes (17.4 ± 6 min for IM and 19.8 ± 7.8 min for SQ). The time of the last quantifiable concentration of buprenorphine was 5 ± 1.67 h for IM compared with 6.33 ± 1.51 h for SQ, which was not statistically different. The mean buprenorphine plasma concentration-time curves were used to propose a dosing frequency of 4 to 6 h for buprenorphine at 0.01 mg/kg IM or SQ based on a theoretical therapeutic plasma concentration threshold of 0.1 ng/mL. Based on the mean pharmacokinetic parameters and plasma-concentration time curves, both IM and SQ routes of buprenorphine at this dose provide a rapid increase in the plasma concentration of buprenorphine above the therapeutic threshold, and may be more effective for acute rather than long-lasting analgesia. Further studies are needed to examine repeated dosing regimens and the efficacy of buprenorphine in common marmosets.

Antibody-drug conjugates (ADCs) combine the specificity of an antibody with the cytotoxicity of a chemical agent. They represent a rapidly evolving area of oncology drug development and hold significant promise. There are currently nine ADCs on the market, more than half of which gained US Food and Drug Administration approval more recently, since 2019. Despite their enormous promise, the therapeutic window for these ADCs remains relatively narrow, especially when compared with other oncology drugs, such as targeted therapies or checkpoint inhibitors. In this review, we provide a detailed overview of the five dosing regimen optimization strategies that have been leveraged to broaden the therapeutic window by mitigating the safety risks while maintaining efficacy. These include body weight cap dosing; treatment duration capping; dose schedule (e.g., dosing frequency and dose fractionation); response-guided dosing recommendations; and randomized dose-finding. We then discuss how the lessons learned from these studies can inform ADC development going forward. Informed application of these dosing strategies should allow researchers to maximize the safety and efficacy for next-generation ADCs.

Medication non-adherence in the elderly population is a major problem, preventing them from obtaining optimal therapeutic effects. Identifying the factors affecting medication adherence is crucial for improving and maintaining health among the elderly population and enhance healthcare economy. The purpose of this study was to examine the prevalence of self-reported medication adherence, and identify the associated factors and the influence of health-related quality of life (HRQOL) in the Japanese community-dwelling elderly population. This cross-sectional study was part of the Nakajima study and targeted inhabitants aged ≥60 years who underwent health examinations in 2017. Data regarding medication adherence were acquired through interviews and self-administered questionnaires. Medication adherence were assessed using a visual analog scale, and HRQOL was assessed by EuroQol five-dimensional questionnaire with 3 levels. Among the 455 participants, low and high medication adherence were seen in 9.7% and 66.2% of the participants, respectively (visual analog scores

Aim:The objective of the present study is to design and characterize the ethosomal gel containing Zaltoprofen for sustained drug delivery and also to reduce the side effects. Zaltoprofen was chosen here as the drug candidate because of its short half-life and increased dosing frequency. Methods: The ethosomes containing Zaltoprofen was prepared by using cold method. A 23 full factorial design containing 10 experimental trails was used in order to obtain an optimized formulation. The prepared ethosomes were characterized by Scanning Electron Microscopy, PDI, zeta potential, vesicle size, and percentage entrapment efficiency. Optimized ethosomal formulation was incorporated in 1% carbopol gel to deliver the drug through topical route. Invitro drug permeation studies of ethosomal gel (EGL) and conventional gel (CGL) was conducted and flux and permeability coefficient were calculated. Results:The vesicle size, zeta potential, and % entrapment efficiency of optimized formulation were found to be 124.33 nm, -45.2 mV and 70.03%, respectively. The surface of the vesicles was found to be spherical and smooth. The in vitro drug release studies of the ethosomal gel formulation showed sustained drug delivery when compared with the conventional gel containing the pure drug. In vitro permeability studies show that the flux of ethosomal gel was 2.5 fold higher than conventional gel, which may be the attribution of ethanol and flexible nature of ethosomes. Conclusion: It was concluded that the ethosomal gel could be a better choice for the topical delivery of Zaltoprofenwith improved bioavailability for its anti-inflammatory activity.

Purpose: We evaluated the relationship between dosing frequency of intravitreal antivascular endothelial growth factor (anti-VEGF) agents and visual acuity (VA) outcomes over 2 years in eyes with macular edema (ME) secondary to central retinal vein occlusion (CRVO) in the US routine clinical practice setting. Methods: This retrospective analysis assessed electronic medical records of eyes with ME secondary to CRVO that received their first anti-VEGF injection January 1, 2012, to May 31, 2016, and were followed for 1 year or more in the US-based Vestrum Health Treatment and Outcomes database. Eyes were divided into 2 injection frequency subcohorts (≤6 or ≥7 injections/year). Results: Overall, 851 (34.6%) of 2458 eyes with ME secondary to CRVO received 6 or fewer injections, and 1607 (65.4%) received 7 or more injections through 1 year. The mean number of injections in patients receiving 6 or fewer injections and 7 or more injections was 4.7 and 8.8, respectively, and baseline mean VA was 35 and 37 letters, respectively. At year 1, mean letter gain from baseline was less in eyes receiving 6 or fewer injections vs in those receiving 7 or more injections (7.0 vs 12.2, P < .001). Mean VA at year 2 was 50 letters in eyes receiving 6 or fewer injections (n = 50) and 55 letters in eyes receiving 7 or more injections (n = 157). Conclusions: In routine clinical practice, more frequent dosing with anti-VEGF agents was associated with greater visual benefits in eyes with ME secondary to CRVO.

Drug-delivery technologies for modified drug release have been in existence for decades, but their utilization has been largely limited to post-launch efforts improving therapeutic outcomes. Recently, they have gained renewed importance because the pharmaceutical industry is steadily shifting to a more integrated discovery-development approach. In discovery, modulating target engagement via drug-delivery technologies can enable crucial pharmacological studies for building well-defined criteria for molecular design. In development, earlier implementation of delivery technologies can enhance the value of drug products through reduced dosing frequency and improved tolerability and/or safety profile, thereby leading to better adherence and therapeutic effectiveness.

Purpose To identify interventions for organizational pharmacist-leaders and frontline pharmacy staff to optimize peri- and postdischarge medication management. Summary An evidence-based toolkit was systematically constructed on the basis of findings of 3 systematic overviews of systematic reviews. The interventions were reviewed by a technical expert panel and categorized as either tools or tactics. The identified tools are instruments such as diagrams, flow charts, lists, tables, and templates used in performing a distinct operation, whereas identified tactics reflect broader methods (eg, reduced dosing frequency). Tools and tactics were chosen on the basis of their potential to improve postdischarge medication management, with a focus on interventions led by pharmacy staff that may reduce hospital readmissions among older, sicker patients. Overall, 23 tools and 2 tactics were identified. The identified tools include items such as education, text messaging, and phone calls. The tactics identified are dose simplification and monetary incentives. Practical information has also been provided to facilitate implementation. Conclusion Several tools and tactics are available to optimize peri- and postdischarge medication management. Organizational pharmacist-leaders and frontline pharmacy staff can implement these interventions to improve patient outcomes.

Buccal drug delivery especially refers to the delivery of drugs through the buccal mucosal membrane lining of the oral cavity. For geriatric and pediatric patients who undergo difficulties in swallowing conventional oral solid dosage forms, the buccal film is a better alternative. The buccal film is appropriate for the drugs which experience high first-pass metabolism and is used for enhancing bioavailability with reducing dosing frequency to mouth plasma peak levels, which thus limit side-effects and make it cost-effective. It enhances the efficacy of API in the oral cavity after the contact with less saliva as contrasted to tablets, without chewing and no need for water for administration. This review briefly describes the advantages and limitations of buccal film, an anatomical structure of oral mucosa, highlighting the mechanisms of drug permeation, formulation technologies, methodology in evaluating buccal film, and recent advances of the buccal film as a tool for drug delivery for various treatments.

Background Direct oral anticoagulants are available for patients with atrial fibrillation. Objective This study compared adherence and persistence of once-daily (QD) vs twice-daily (BID) direct oral anticoagulants in patients with atrial fibrillation. Methods A cohort study was conducted in three databases in the Netherlands, Italy and Germany. Patients with AF starting direct oral anticoagulants after drug approval date were included. The index date was the date of first dispensing. Study patients were restricted to those aged >= 18 years, >= 1 year database history and >= 1 year follow-up. Adherence to treatment was defined as the proportion of days covered >= 80% between the index date and the date of last dispensing of the index regimen (i.e. exposure period). The proportion of days covered was also determined during the 12-month follow-up. Persistence was defined as continuous use from index to treatment discontinuation. Results In the Netherlands, Italy and Germany, respectively, 6068, 32,260 and 167,445 patients were included. The mean age of the patients was 70, 77 and 74 years, and 31%, 40% and 61% were QD users, all respectively. Among QD/BID users, 93/90%, 88/86% and 77/58%, respectively were adherent during the exposure period. Persistence rates at 1 year in QD/BID users were 60/59%, 13/14% and 46/31%, respectively. Conclusions Adherence to treatment was high. In Germany, adherence was markedly higher in QD users compared with BID users. In Italy and the Netherlands, these differences were marginal. Persistence was low in all countries, but discontinuation was temporary. Only in Germany, persistence was markedly lower in BID users vs QD users.

Purpose: This work evaluates dosing frequency with intravitreal antivascular endothelial growth factor (anti-VEGF) agents over 2 years and visual acuity (VA) outcomes in neovascular age-related macular degeneration (nAMD). Methods: This retrospective analysis assesses electronic medical record data (Vestrum Health treatment and outcomes database) of newly diagnosed nAMD in patients who were initiated on intravitreal anti-VEGF treatment at US clinical sites. Eyes were divided into 2 injection frequency subcohorts (≤ 6 or > 6 injections/y); treatment frequency and change in mean VA (Early Treatment Diabetic Retinopathy Study letters) were evaluated. Results: Overall, 8127 of 213 824 eyes met inclusion criteria in year 1 and 4968 in year 2. During year 1, 77% of the eyes received more than 6 injections (n = 6287), the majority of which received injections at the same frequency during year 2. Mean VA gain from baseline at year 1 was lower in the ≤ 6 than > 6 injections/y subcohort (2.2 vs 6.5, P < .001). Decrease in mean VA from the end of year 1 to year 2 was significantly greater for eyes administered 6 or fewer injections in year 2 than those that received more frequent injections, irrespective of the frequency of injections in the first year. Conclusions: In routine clinical practice, most eyes with nAMD that completed at least 1 year of follow-up were treated with more than 6 injections of anti-VEGF agents during the first year of treatment, resulting in better VA gains than eyes treated less frequently during the same period.

Delamanid is a poorly water-soluble drug currently being used for the treatment of tuberculosis. The high frequency of dosing leads to poor adherence for patients who live in lower economic and nomadic populations. Non-digestible self-assembling lipids as a formulation approach for poorly water-soluble drugs have previously been shown to extend the window of absorption through gastric retention. We hypothesise that this approach could lead to the reduction of dosing frequency for delamanid and thereby has potential to improve adherence. Formulations of delamanid were prepared in selachyl alcohol and phytantriol as non-digestible self-assembling lipid vehicles, and their behaviour was compared with reconstituted milk powder, as a digestible lipid-based formulation, and an aqueous suspension. The self-assembly of selachyl alcohol and phytantriol in aqueous media in the presence of delamanid was studied using small angle X-ray scattering and produced the inverse hexagonal (H2) and inverse bicontinuous cubic (V2) liquid crystal structures, respectively. The times at which maximum delamanid levels in plasma were observed (Tmax) after oral administration of the phytantriol, selachyl alcohol and reconstituted milk powder formulations of delamanid to rats were 27 ± 3, 20 ± 4 and 6.5 ± 1.0 h, respectively, compared with the aqueous suspension formulation with a Tmax of 3.4 ± 1 h, which confirms the hypothesis of an extended duration of absorption after administration in non-digestible self-assembling lipids. The digestion products of the triglycerides in the milk formulation increased the solubilisation of delamanid in the gastrointestinal tract, leading to an increase in exposure compared with the aqueous suspension formulation but did not significantly extend Tmax. Overall, the non-digestible nanostructured lipid formulations extended the duration of absorption of delamanid well beyond that from milk or suspension formulations. Graphical abstract Electronic supplementary material The online version of this article (10.1007/s13346-020-00851-z) contains supplementary material, which is available to authorized users.

Present investigation was aimed to develop Aspasomal gel of Mometasone Furoate for the treatment Psoriasis and deliver drug at controlled rate and decrease dosing frequency. The vesicles were fabri...

Objective The number of therapies for axial spondyloarthritis (axSpA) is increasing. Thus, it has become more challenging for patients and physicians to navigate the risk-benefit profiles of the various treatment options. In this study, we used conjoint analysis-a form of trade-off analysis that elucidates how people make complex decisions by balancing competing factors-to examine patient decision-making surrounding medication options for axSpA. Methods We conducted an adaptive choice-based conjoint analysis survey for patients with axSpA to assess the relative importance of medication attributes (eg, chance of symptom improvement, risk of side effects, route of administration, etc) in their decision-making. We also performed logistic regression to explore whether patient demographics and disease characteristics predicted decision-making. Results Overall, 397 patients with axSpA completed the conjoint analysis survey. Patients prioritized medication efficacy (importance score 26.8%), cost (26.3%), and route of administration (13.9%) as most important in their decision-making. These were followed by risk of lymphoma (9.5%), dosing frequency (7.2%), risk of serious infection (6.0%), tolerability of side effects (5.3%), and clinic visit and laboratory test frequency (4.8%). In regression analyses, there were few significant associations between patients' treatment preferences and sociodemographic and axSpA characteristics. Conclusions Treatment decision-making in axSpA is highly individualized, and demographics and baseline disease characteristics are poor predictors of individual preferences. This calls for the development of online shared decision-making tools for patients and providers, with the goal of selecting a treatment that is consistent with patients' preferences.

Objective To determine the tear film levels of oxytetracycline in normal canine eyes after application of the ophthalmic ointment, Terramycin™ (0.5% oxytetracycline, polymyxin B sulfate), to guide appropriate treatment frequency. Animals studied Ten research beagles. Procedures Ten research beagles with confirmed normal eyes were administered 0.02 mL of Terramycin™ ophthalmic ointment onto the dorsal bulbar conjunctival surface of the right eye. Tear samples were collected via dye-less Schirmer tear strips at 2, 4, 6, 8, and 12 hours post-administration. The sample for each timepoint was collected on a separate day, and concentrations of oxytetracycline were determined using high-performance liquid chromatography (HPLC). Results There was a semi-logarithmic decline in the median tear concentration of oxytetracycline. The median (2.5th and 97.5th percentiles) tear concentrations of oxytetracycline at 2, 4, 6, 8, and 12 hours were 43.5 μg/mL (11.1-302.2 μg/mL), 28.7 μg/mL (8.04-113.7 μg/mL), 16.1 μg/mL (4.96-37.7 μg/mL), 9.2 μg/mL (4.52-28.1 μg/mL), and 6.11 μg/mL (4.36-26.7 μg/mL), respectively. Mean (±SD) drug recovery via HPLC was 88% (±7.5%). Conclusions Ophthalmic Terramycin™ achieves a substantially higher tear level than the MIC for common bacterial corneal pathogens up to 12 hours post-administration in normal eyes. Anti-collagenolytic tear levels were not achieved at the timepoints evaluated or with the manufacturer-prescribed dosing frequency. HPLC can be used to analyze tear concentrations of ophthalmic ointment formulations.

Aim Psychopharmacological treatment is indispensable in patients with schizophrenia but data on needs, preferences, and complaints about their medications are limited. Moreover, there has been no study to assess the degree of awareness of their psychiatrists (gap in needs) regarding these issues. Methods Ninety‐seven Japanese patients with schizophrenia (ICD‐10) were asked to fill in the questionnaire consisting of multiple‐choice questions regarding (a) their needs and complaints about psychopharmacological treatment that they were receiving, and (b) their preference of dosage form, dosing frequency, and timing of dosing. Additionally, their psychiatrists in charge were asked to predict their patients’ response to the above questions. Results Both the most frequently endorsed need and complaints about the current psychopharmacological treatment were “nothing in particular” (n = 14, 16.7% and n = 17, 20.2%); merely 23.1% and 15.4% of their psychiatrists correctly predicted these responses, respectively. “Once a day” (n = 56, 65.1%), “at bedtime” (n = 53, 61.6%), and “tablet” (n = 51, 59.3%) were the patients’ most favorite dosing frequency, timing, and dosage form, respectively; 59.8% (n = 49), 54.9% (n = 45), and 64.6% (n = 53) of their psychiatrists predicted them. Conclusions These findings suggest that there is substantial room for improvement on the side of psychiatrists to capture their patients’ needs and complaints about psychopharmacological treatment.

Hydrogels are aqueous gels composed of cross-linked networks of hydrophilic polymers. Stimuli-responsive based hydrogels have gained focus over the past 20 years for treating ophthalmic diseases. Different stimuli-responsive mechanisms are involved in forming polymer hydrogel networks, including change in temperature, pH, ions, and others including light, thrombin, pressure, antigen, and glucose-responsive. Incorporation of nanocarriers with these smart stimuli-responsive drug delivery systems that can extend the duration of action by increasing ocular bioavailability and reducing the dosing frequency. This review will focus on the hydrogel drug delivery systems highlighting the gelling mechanisms and emerging stimuli-responsive hydrogels from preformed gels, nanogels, and the role of advanced 3D printed hydrogels in vision-threatening diseases like age-related macular degeneration and retinitis pigmentosa. It also provides insight into the limitations of hydrogels along with the safety and biocompatibility of the hydrogel drug delivery systems.

Objectives To report interim data from TAURUS, a study assessing real-world prophylactic treatment with unmodified, full-length recombinant FVIII BAY 81-8973 (Kovaltry(R); Bayer) indicated for haemophilia A. Methods TAURUS (NCT02830477) is an international, open-label, prospective, non-interventional, single-arm study with a one-year observation period (target N = 350). Patients have moderate or severe haemophilia A (FVIII = 50 exposure days to any FVIII product. Clinician- and patient-reported outcomes are captured on previous product use, changes in prophylaxis dose and dosing frequency, FVIII consumption, reported bleeding rates, treatment satisfaction and adherence, pharmacokinetic (PK) data (if available) and safety data. Results At cut-off, baseline data were available from 160 patients (89 had >= 6 months of follow-up data). Most patients had severe haemophilia A (85%), infused BAY 81-8973 >= 3x/wk (59%) and experienced a median number of total bleeds of 2.0 (non-annualised; 246 days median documentation period). Good levels of treatment satisfaction (Hemo-SAT(A,P)) and adherence (VERITAS-Pro) were maintained. TAURUS demonstrated a favourable PK profile of BAY 81-8973 in comparison with other standard half-life rFVIIIs and supported the WAPPS PopPK model. No patients developed inhibitors. Conclusions TAURUS data demonstrate effective prophylaxis with BAY 81-8973 in the real world without compromising patient satisfaction or adherence.

Parkinson's Disease (PD) is effecting 7-10 million people of worldwide as the report of WHO 2014. It has proved to be 2 nd most a neuro-degenerative disorder of the central nervous system (CNS). It occurs due to the death of dopamine-generating cells in the substantia-nigra, a region of the midbrain. It is characterized by tremor, rigidity, bradykinesia, dementia, depression and falls or emerges with the progression of the disease. Ropinirole HCl is a low molecular weight, highly water soluble drug. It is rapidly absorbed from the G.I.T and mean peak plasma concentrations have been achieved within 1.5 h after oral doses. The oral bioavailability of Ropinirole HCl is 50% due to extensive first pass metabolism by the liver. Its mean plasma half-life is 5–6 h. The present study tries to enlighten the prior art related to Parkinson's treatment and to prepare Ropinirole HCl loaded Nano-structured lipid carriers (NLC) that may overcome the problem of bioavailability and bypass the blood brain barrier by preparing the intra-nasal drug delivery targeted to the brain thereby decreasing the dosing frequency and increasing patient compliance. Keywords: Parkinson's Disease, Bioavailability, NLC, Nano-technology.

Objective To evaluate real‐world outcomes with rVIII‐SingleChain and other commonly used recombinant FVIII (rFVIII) products. Methods Hemophilia treatment centers in Germany (n = 21) contributed patient chart data. Inclusion criteria were prophylactic treatment with one of five rFVIII products for ≥8 weeks. Results Male patients (n = 225) were included: rVIII‐SingleChain (n = 40), rFVIIIFc (n = 47), octocog alfa (rFVIII; n = 58), octocog alfa (BAY 81‐8973; n = 40), or moroctocog alfa (n = 40). In patients with severe disease (n = 76), 66.6%, 70.0%, 20.0%, 7.7%, and 27.3% were dosed ≤2×/week, respectively. Irrespective of dosing frequency, mean annualized bleed rates (ABRs)/annualized spontaneous bleed rates (AsBRs) were 0.3/0.1, 0.8/0.4, 1.1/0.5, 1.5/0.8, and 1.4/0.6, and mean FVIII consumption (IU/kg/week) was 83.2, 97.2, 92.5, 104.0, and 102.1, respectively. Results for all patients were similar. Of the patients on prophylaxis with prior therapy and after switching to rVIII‐SingleChain (n = 21), mean ABR/AsBRs were 0.7/0.3 and 0.2/0.0, respectively. After switching to rVIII‐SingleChain, mean FVIII consumption reduced (109.4 vs 74.5 IU/kg/week), and percentage of patients dosed ≤2×/week increased (0% to 71.4%). Conclusions rVIII‐SingleChain prophylaxis provides excellent bleeding protection, with potentially lowest factor consumption among the products assessed. Patients who switched to rVIII‐SingleChain prophylaxis reduced dosing frequency and consumption compared with prior treatment, with similar or potentially lower bleeding rates.

Advanced drug delivery systems such as liposomes, niosomes, ethosomes and phytosomes significantly influence the quality of synthetic drug formulations. However, the trend is now shifting towards natural-based moieties, most probably because of their promising therapeutic responses, and considerably lower incidence of side effects and toxicity issues. The effectiveness of herbal plant formulations in nano-sized particles in the delivery of active compounds is increased since nanoparticles offer a larger surface area and promote longer contact time with the surfaces of the targeted sites. Thus, nanoparticles allow the sustained release of small amounts of active compounds and the optimization of the dosing frequency of the drug. The implementation of nanotechnology in the development of natural-based products is able to enhance the delivery of plant extracts and active phytochemicals to the targeted sites. In fact, maximum therapeutic outcomes can be achieved since the herbal formulations are more stable compared to traditional preparations. The development of herbal formulations in modern drug delivery systems will be further discussed in this review. The possible improvement of phytosomes is highlighted in order to give future insights into improvising phytosomes as a targeted drug carrier system. A compilation of evidence-based studies involving the nanotechnology of herbal formulations is summarized accordingly. The use of modern technology in herbal drug delivery systems has been growing in past decades and needs to be further explored by scientists. Hence, at the end of this review, a brief summary is given of a few success stories regarding modern nano formulations that have been commercialized by leading herbal companies and which can be considered as great achievements in this field. Thus, this review is aimed at exploring the use of nanotechnology in drug delivery systems and discusses their contribution to the design of modern herbal formulations.

Diabetes mellitus is a chronic disease in which there is an insufficient production of insulin by the pancreas, or the insulin produced is unable to be utilized effectively by the body. Diabetes affects more than 415 million people globally and is estimated to strike about 642 million people in 2040. The WHO reported that diabetes will become the seventh biggest cause of mortality in 2030. Insulin injection and oral hypoglycemic agents remain the primary treatments in diabetes management. These often present with poor patient compliance. However, over the last decade, transdermal systems in diabetes management have gained increasing attention and emerged as a potential hope in diabetes management owing to the advantages that they offer as compared to invasive injection and oral dosage forms. This review presents the recent advances and developments in transdermal research to achieve better diabetes management. Different technologies and approaches have been explored and applied to the transdermal systems to optimize diabetes management. Studies have shown that these transdermal systems demonstrate higher bioavailability compared to oral administration due to the avoidance of first-pass hepatic metabolism and a sustained drug release pattern. Besides that, transdermal systems have the advantage of reducing dosing frequency as drugs are released at a predetermined rate and control blood glucose level over a prolonged time, contributing to better patient compliance. In summary, the transdermal system is a field worth exploring due to its significant advantages over oral route in administration of antidiabetic drugs and biosensing of blood glucose level to ensure better clinical outcomes in diabetes management., Graphical abstract Microneedles are the most extensively studied transdermal drug delivery systems in diabetes management. With microneedles forming the basis of the drug delivery systems, different technologies have also been employed to enhance the functionality and properties of transdermal patch.Image, graphical abstract

Implantable and long-lasting drug delivery systems provide sustained delivery of drug over a period of weeks to months. These systems can provide many advantages in the delivery of drugs for conditions in which the patient is required to take medications frequently for an indefinite period of time, such as less frequent dosing and improved quality of life. This chapter will cover infectious, inflammatory, endocrine, and neurodegenerative diseases. In the majority of these diseases, frequent dosing is required by the patient, leading to poor adherence by them. Therefore long-acting implants and systems are evaluated as novel methods for drug delivery, which can reduce dosing frequency and improve patient adherence, in turn improving efficacy of treatment.

Objective: To report a case of hyperammonemia associated with the interaction between topiramate and valproic acid. Case Summary: We present a patient case with topiramate-related hyperammonemia. The patient was on topiramate prior to admission and presented with an elevated ammonia level following 2 doses of valproic acid. The increased dosing frequency of valproic acid further exacerbated the hyperammonemia. On discontinuation of topiramate and the tapering of the dose of valproic acid the patient’s ammonia level returned to normal. Discussion: Valproic acid–induced hyperammonemic encephalopathy is well documented and there are several proposed mechanisms. The interaction between valproic acid and topiramate causing drug-induced hyperammonemia encephalopathy is documented in several case reports. The interaction is associated with the addition of topiramate to a patient’s medication regimen that previously included valproic acid. Topiramate also has several proposed mechanisms for predisposing patients for hyperammonemia. There are limited data on topiramate monotherapy or long-term use of topiramate use causing hyperammonemia-associated encephalopathy or enhancing hyperammonemia with the addition of valproic acid. Conclusions: This case supports topiramate-related hyperammonemia and the pharmacodynamic interaction with the co-administration of valproic acid.

A clinical decision report using: Fife KH, Ferenczy A, Douglas JM Jr, et al. Treatment of external genital warts in men using 5% imiquimod cream applied three times a week, once daily, twice daily, or three times a day. Sex Transm Dis. 2001;28(4):226-231. https://doi.org/10.1097/00007435-200104000-00007 for a patient with genital warts and an unstable social support network.