High Dosing Frequency Research Articles

Benchmarking the medication efficiency and technological progress of diabetes drugs

BackgroundDiabetes poses a serious global challenge, given its increasing prevalence, detrimental effects on public health, and substantial economic burden. Since 1950s, tens of drugs have been approved by the United States (US) Food and Drug Administration (FDA). In the past decade, the medical community and regulatory agencies have moved away from the glucose-centric paradigm and increasingly call for a holistic approach to assess different treatments’ benefits and harms.ObjectiveThis study aimed to assess the medication efficiency and technological progress of Type 2 Diabetes (T2D) drugs, by considering their physiological outcomes, including both benefits (i.e., glucose lowering and weight loss) and adverse effects (mortality), relative to dosing frequency.MethodsTo derive medication efficiency, this study utilized data from the US FDA and prominent meta-analyses. Given that both the benefits and adverse effects of medications are multidimensional, this study employed a nonparametric frontier method, the data envelopment analysis (DEA) model, to integrate these factors into a measure of medication efficiency. Physiological outcomes could assume both positive and negative values. Adverse effects were regarded undesirable outputs. The DEA model was built under the framework of directional distance function and was able to handle negative and undesirable values which naturally arose in the case of T2D medications.ResultsThe paper presented a ranking of 20 T2D drugs in terms of medication efficiency. Three of them were able to attain the highest medication efficiency, all of which were in the GLP-1 class, including oral Semaglutide, subcutaneous Semaglutide and Dulaglutide. However, the other two GLP-1 drugs, Lixisenatide and Liraglutide, were less efficient. The average medication efficiency of drugs approved post-2010 was significantly higher than pre-2010 drugs. High dose frequency, low HbA1c reduction and insignificant weight loss were the main driving factors behind inefficiencies. Overall, medication efficiency provided an alternative perspective on treatment effectiveness other than conventional measures such as cost-effectiveness.

Mimosa/quince seed mucilage–co-poly (methacrylate) hydrogels for controlled delivery of capecitabine: Simulation studies, characterization and toxicological evaluation

This research focused on developing pH-regulated intelligent networks using quince and mimosa seed mucilage through aqueous polymerization to sustain Capecitabine release while overcoming issues like short half-life, high dosing frequency, and low bioavailability. The resulting MSM/QSM-co-poly(MAA) hydrogel was evaluated for several parameters, including complex structure formation, stability, pH sensitivity, morphology, and elemental composition.FTIR, DSC, and TGA analyses confirmed the formation of a stable, complex cross-linked network, demonstrating excellent stability at elevated temperatures. SEM analysis revealed the hydrogels' smooth, fine texture with porous surfaces. PXRD and EDX results indicated the amorphous dispersion of Capecitabine within the network.The QMM9 formulation achieved an optimal Capecitabine loading of 87.17 %. The gel content of the developed formulations ranged from 65.21 % to 90.23 %. All formulations exhibited excellent swelling behavior, with ratios between 65.91 % and 91.93 % at alkaline pH. In vitro dissolution studies indicated that up to 98 % of Capecitabine was released after 24 h at pH 7.4, demonstrating the potential for sustained release.Furthermore, toxicological evaluation in healthy rabbits confirmed the system's safety, non-toxicity, and biocompatibility.

The Feasibility of an Online Language Program Delivered Through Music and the Impact of Dosage on Vocabulary Outcomes in Young Children With Down Syndrome.

Few studies have explored the feasibility of online language interventions for young children with Down syndrome. Additionally, none have manipulated dose frequency or reported on the use of music as a medium through which language and sign can be learned. The purpose of this study was to (a) examine the feasibility and acceptability of an online language through music intervention for young children (1-3;6 years) with Down syndrome and (b) compare effectiveness at two intervention dose frequencies. The study was carried out in two phases using a mixed-methods design. Phase 1: Qualitative data were gathered from parents to examine feasibility when implementing a video-based language intervention. Phase 2: Seventy-six families participated in an online language intervention at home. Effectiveness was examined comparing two groups, randomly assigned to a high and low dose frequency. The Down Syndrome Education (DSE) checklists (combined) were the primary outcome measure. Process data were gathered to determine intervention acceptability in practice and to identify factors that would improve successful future implementation. Acceptability data were analyzed with reference to the theoretical framework of acceptability (Version 2). Forty-three parents completed the Phase 1 scoping questionnaire, five of whom took part in focus groups. Once weekly morning sessions were indicated as the preferred scheduling choice. Phase 2 quantitative data were analyzed using beta regression adjusted for baseline scores and indicated no additional benefit to receiving the higher dose. However, exploratory interaction models suggested that the efficacy of the high-dose intervention was higher (than low-dose intervention) in participants with higher baseline DSE performance. Parents perceived the intervention to be effective and positive for the family. The results add to our knowledge of real-world effective online interventions and suggest that a critical minimum language level is required for children with Down syndrome to benefit optimally from a higher intervention dose frequency. https://doi.org/10.23641/asha.25979704.

In vitro and in vivo evaluation of isoxsuprine loaded invasomes for efficient treatment of diabetes‐accelerated atherosclerosis

Hyperglycemia in diabetes mellitus exacerbates vascular disarray in atherosclerosis by damaging endothelial cells and vascular smooth muscles. It's a major contributor to deaths from cardiovascular disease. Isoxsuprine (IXS) is an oral beta-adrenergic agonist that improves arterial blood flow due to its vasodilatation effect and boosts insulin secretion. However, oral IXS has low efficacy, low bioavailability and patient incompliance due to its high dose frequency, short biological half-life and fast clearance. The goal of this research was to develop a nasal formulation of IXS-loaded invasomes to sustain IXS's release and improve its permeation and efficacy as a potential diabetes-accelerated atherosclerosis treatment. Different IXS-loaded invasomes formulations were developed using design expert software to study the effects of ethanol, phospholipid, and cineole concentrations. Based on the desirability index, the formulation with 1 % ethanol, 0.5 % cineole, and 2.48 % phospholipid was chosen as the optimum formulation. The optimum IXS-loaded invasomes formulation showed an encapsulation efficiency of 72.03 % and a particle size of 210.26 nm. Production of nasal IXS-loaded invasomes formulation increased the permeation of IXS with a ratio of 2.25 and sustained its release. The optimum IXS-loaded invasomes formulation was non-cytotoxic and showed a good binding mode with serum proteins. When optimum IXS-loaded invasomes formulation was evaluated in vivo against a rat model of experimental diabetes and atherosclerosis, it showed anti-diabetic and anti-atherosclerotic effects. It substantially increased the levels of HDL by 45.11 % and substantially decreased the levels of glucose, LDL, triglycerides, and cholesterol by 41.35 %, 89.76 %, 51.01 %, and 60.18 %, respectively. Histopathology also showed that atherosclerotic lesions got improved in rats given optimum IXS-loaded invasomes formulation. In conclusion, nasal administration of IXS-loaded invasomes could be a potential diabetes-accelerated atherosclerosis treatment.

Two Sustained Release Membranes Used in Formulating Low Strength Testosterone Reservoir Transdermal Patches.

Several Testosterone Replacement Therapies exist for hypogonadism, but an in-depth analysis of these products reveals a high dosing frequency and a high drug loading, up to 120 mg for a potent drug like Testosterone. This may lead to patient non-compliance and toxicity problems if used improperly. Androderm® is the only 24-hour marketed transdermal patch. Testopel pellets are another extended-release product given subcutaneously every 3-6 months. But it requires surgical implantation and is associated with severe adverse effects. For this reason, the development of other extended- release testosterone products is needed. The study aims at using different excipients for the exploration of sustained-release patches. Reservoir formulations were prepared using Carbomer 941 and HPMC K100M as the sustained- release polymers plus CoTran™ 9702 and CoTran™ 9712 as the release membranes. The formulated patches were subjected to in vitro dissolution for 24 h. The amount of drug release at each time point was determined using the developed HPLC assay. FDA Similarity Factor, f2, t-test, and ANOVA were applied to all nine-point collected samples. CoTran™ 9712 membrane was found to be a better candidate than CoTran™ 9702. The in vitro release profiles of the four formulations were compared (Carbomer vs. HPMC, and CoTran™ 9702 vs. CoTran™ 9712). CoTran™ 9702 releases testosterone significantly lower. Carbomer and CoTran™ 9712 were the best formulation among all with the highest drug release of 2.16 ± 0.36 mg.

Vesicular Nanocarriers: A Potential Platform for Topical/Transdermal Delivery of Antibiotics.

Bacterial infections are becoming difficult to treat nowadays due to the development of resistance towards conventional treatments. Conventional topical formulations loaded with antibiotics display various disadvantages, like high dosing frequency, high toxicity, and poor patient compliance. The former limitations may sometimes lead to severe complications and hospitalization of patients. However, these can be overcome by employing vesicular nanocarriers for the delivery of antibiotics following the topical/transdermal route. The objective of this review paper was to summarize the role of vesicular nanocarriers, like liposomes, elastic liposomes, niosomes, ethosomes, solid lipid nanoparticles, nanostructured lipid carriers, and nanoemulsions for topical/transdermal delivery of antibiotics, and patents associated with them. Literature for the present review was collected using various search engines, like PubMed, Google Scholar, and Google Patents. Various literature investigations have revealed the in vitro and preclinical efficacy of vesicular nanocarrier systems in the delivery of antibiotics following the topical/transdermal route. Vesicular nanocarrier systems, via targeted delivery, may subside various side effects of antibiotics associated with conventional delivery, like high dosing frequency and poor patient compliance. However, their existence in the pharmaceutical market will be governed by effective clinical assessment and scale-up methodologies.

Prodrugs as empowering tools in drug discovery and development: recent strategic applications of drug delivery solutions to mitigate challenges associated with lead compounds and drug candidates.

The delivery of a drug to a specific organ or tissue at an efficacious concentration is the pharmacokinetic (PK) hallmark of promoting effective pharmacological action at a target site with an acceptable safety profile. Sub-optimal pharmaceutical or ADME profiles of drug candidates, which can often be a function of inherently poor physicochemical properties, pose significant challenges to drug discovery and development teams and may contribute to high compound attrition rates. Medicinal chemists have exploited prodrugs as an informed strategy to productively enhance the profiles of new chemical entities by optimizing the physicochemical, biopharmaceutical, and pharmacokinetic properties as well as selectively delivering a molecule to the site of action as a means of addressing a range of limitations. While discovery scientists have traditionally employed prodrugs to improve solubility and membrane permeability, the growing sophistication of prodrug technologies has enabled a significant expansion of their scope and applications as an empowering tool to mitigate a broad range of drug delivery challenges. Prodrugs have emerged as successful solutions to resolve non-linear exposure, inadequate exposure to support toxicological studies, pH-dependent absorption, high pill burden, formulation challenges, lack of feasibility of developing solid and liquid dosage forms, first-pass metabolism, high dosing frequency translating to reduced patient compliance and poor site-specific drug delivery. During the period 2012-2022, the US Food and Drug Administration (FDA) approved 50 prodrugs, which amounts to 13% of approved small molecule drugs, reflecting both the importance and success of implementing prodrug approaches in the pursuit of developing safe and effective drugs to address unmet medical needs.

Quince seed mucilage/β-cyclodextrin/Mmt-Na+-co-poly (methacrylate) based pH-sensitive polymeric carriers for controlled delivery of Capecitabine

In current work, quince seed mucilage and β-Cyclodextrin based pH regulated hydrogels were developed using aqueous free radical polymerization to sustain Capecitabine release patterns and to overcome its drawbacks, such as high dose frequency, short half-life, and low bioavailability. Developed networks were subjected to thermal analysis, Fourier transforms infrared spectroscopy, powder x-ray diffraction, elemental analysis, scanning electron microscopy, equilibrium swelling, and in-vitro release investigations to assess the network system's stability, complexation, morphology, and pH responsiveness. Thermally stable pH-responsive cross-linked networks were formed. Nanocomposite hydrogels were prepared by incorporating Capecitabine-containing clay into the swollen hydrogels. All the formulations exhibited equilibrium swelling ranging from 67.98 % to 92.98 % at pH 7.4. Optimum Capecitabine loading (88.17 %) was noted in the case of hydrogels, while it was 74.27 % in nanocomposite hydrogels. Excellent gel content (65.88 %–93.56 %) was noticed among developed formulations. Elemental analysis ensured the successful incorporation of Capecitabine.Nanocomposite hydrogels released 80.02 % longer than hydrogels after 30 h. NC hydrogels had higher t1/2 (10.57 h), AUC (121.52 μg.h/ml), and MRT (18.95 h) than hydrogels in oral pharmacokinetics. These findings imply that the pH-responsive carrier system may improve Capecitabine efficacy and reduce dosing frequency in cancer therapy. Toxicity profiling proved the system's safety, non-toxicity, and biocompatibility.

Natamycin Ocular Delivery: Challenges and Advancements in Ocular Therapeutics.

Fungal keratitis, an ocular fungal infection, is one of the leading causes of monocular blindness. Natamycin has long been considered the mainstay drug used for treating fungal keratitis and is the only US Food and Drug Administration (USFDA)-approved drug, commercially available as a topical 5% w/v suspension. Furthermore, ocular fungal infection treatment takes a few weeks to months to recover, and the available marketed antifungal suspensions are associated with poor residence time, limited bioavailability (< 5%) and high dosing frequency as well as minor irritation and discomfort. Despite these challenges, natamycin is still the preferred drug choice for treating fungal keratitis, as it has fewer side effects and less ocular toxicity and is more effective against Fusarium species than other antifungal agents. Several novel therapeutic approaches for the topical delivery of natamycin have been reported to overcome the challenges posed by the conventional dosage forms and to improve ocular bioavailability for the efficient management of fungal keratitis. Current progress in the delivery systems uses approaches aimed at improving the corneal residence time, bioavailability and antifungal potency, thereby reducing the dose and dosing frequency of natamycin. In this review, we discuss the various strategies explored to overcome the challenges present in ocular drug delivery of natamycin and improve its bioavailability for ocular therapeutics.

Dose frequency randomized controlled trial for Dynamic Temporal and Tactile Cueing (DTTC) treatment for childhood apraxia of speech: protocol paper

BackgroundChildhood apraxia of speech (CAS) is a pediatric motor-based speech sound disorder that requires a specialized approach to intervention. The extant literature on the treatment of CAS commonly recommends intensive treatment using a motor-based approach, with some of the best evidence supporting the use of Dynamic Temporal and Tactile Cueing (DTTC). To date, a rigorous and systematic comparison of high and low dose frequency (i.e., frequency of therapy sessions) has not been undertaken for DTTC, resulting in a lack of evidence to guide decisions about the optimal treatment schedule for this intervention. The current study aims to fill this gap in knowledge by comparing treatment outcomes when dose frequency is varied.MethodsA randomized controlled trial will be conducted to examine the efficacy of low versus high dose frequency on DTTC treatment outcomes in children with CAS. A target of 60 children, 2;6–7;11 years of age, will be recruited to participate in this study. Treatment will be provided in the community setting by speech-language pathologists who have completed specialized training administering DTTC in a research reliable manner. True randomization with concealed allocation will be used to assign children to either the low or high dose frequency group. Treatment will be administered in 1-h sessions either 4 times per week over a 6-week period (high dose) or 2 times per week over a 12-week period (low dose). To measure treatment gains, probe data will be collected before treatment, during treatment, and 1 day, 1 week, 4 weeks, and 12 weeks post-treatment. Probe data will consist of customized treated words and a standard set of untreated words to assess generalization of treatment gains. The primary outcome variable will be whole word accuracy, encompassing segmental, phonotactic, and suprasegmental accuracy.DiscussionThis will be the first randomized controlled trial to evaluate dose frequency for DTTC treatment in children with CAS.Trial registrationClinicalTrials.gov identifier NCT05675306, January 6, 2023.

Natural Compounds, Optimal Combination of Brusatol and Polydatin Promote Anti-Tumor Effect in Breast Cancer by Targeting Nrf2 Signaling Pathway.

Triple-negative breast cancer (TNBC) has been clearly recognized as a heterogeneous tumor with the worst prognosis among the subtypes of breast cancer (BC). The advent and application of current small-molecule drugs for treating TNBC, as well as other novel inhibitors, among others, have made treatment options for TNBC more selective. However, there are still problems, such as poor patient tolerance, large administration doses, high dosing frequency, and toxic side effects, necessitating the development of more efficient and less toxic treatment strategies. High expression of Nrf2, a vital antioxidant transcription factor, often promotes tumor progression, and it is also one of the most effective targets in BC therapy. We found that in MDA-MB-231 cells and SUM159 cells, brusatol (BRU) combined with polydatin (PD) could significantly inhibit cell proliferation in vitro, significantly downregulate the expression of Nrf2 protein as well as the expression of downstream related target genes Heme Oxygenase-1 (HO-1) and NAD(P)H dehydrogenase, quinone 1 (NQO1), and promote reactive oxygen species (ROS) levels to further strengthen the anti-tumor effect. Furthermore, we discovered in our in vivo experiments that by reducing the drug dosage three times, we could significantly reduce tumor cell growth while avoiding toxic side effects, providing a treatment method with greater clinical application value for TNBC treatment.

Perspectives on Parkinson’s Disease Medications: A Qualitative Study of People with Parkinson’s Disease (P14-11.015)

<h3>Objective:</h3> To explore the thoughts, beliefs, and expectations of people with Parkinson’s disease (PwPD) regarding their Parkinson’s disease (PD) medications. <h3>Background:</h3> Few studies investigate the factors that inform the impact of PD medications on individuals’ lives. This qualitative study aims to better understand PwPD’s experiences with and perspectives on their medications. <h3>Design/Methods:</h3> PwPD treated with PD medications at five movement disorder clinics in five states across the United States were recruited to participate in semi-structured interviews (SSIs) and focus groups (FGs). Interview and moderator guides developed to explore participants’ experiences with PD medication were utilized. Inclusion criteria consisted of confirmed PD diagnosis, history of taking medications for PD, aged ≥18 years, and ability to consent and participate. SSI and FG transcripts were analyzed via grounded theory methodology to identify primary themes and subthemes. <h3>Results:</h3> Twenty PwPD (8 females/12 males; aged 48–80 years) participated in one-hour telephone SSIs and 32 (16 females/16 males; aged 57–86 years) participated in one-hour online FGs. Four primary themes (subthemes in parentheses) emerged regarding medications for PD: (1) effectiveness (effectiveness uncertainty, expectation realignment), (2) side effects (tolerating side effects, discerning side effects vs disease progression), (3) timing challenges (dosage timing, off-times), and (4) desires (more options, therapy advancement). Participants were uncertain whether they were experiencing the full benefits of their medications and unsure of whether their symptoms were medication side effects or signs of disease progression. High dosing frequency is especially taxing on PwPD, and participants expressed a desire for longer-lasting medications and more therapeutic options. <h3>Conclusions:</h3> This study identified four core dimensions of PD medications from the perspective of PwPD. Results indicate the need for enhanced communication between providers and patients regarding PD medication to reduce uncertainties around symptom burden, and continued efforts to develop and advance PD treatments. <b>Disclosure:</b> Dr. Richards has received research support from Cerevel Therapeutics. Dr. Brown has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Taiho. Dr. Brown has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Patient Centered Outcomes Research Institute (PCORI). The institution of Dr. Brown has received research support from National Comprehensive Cancer Network/Pfizer. The institution of Dr. Brown has received research support from American Society of Clinical Oncology/Pfizer. The institution of Dr. Brown has received research support from Cerevel Therapeutics . Dr. Johnsrud has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Atlas Clarity. Dr. Johnsrud has stock in NuCara Management Group. The institution of Dr. Johnsrud has received research support from Cerevel Therapeutics. Dr. Arcona has received personal compensation for serving as an employee of Cerevel. Dr. Arcona has stock in Cerevel. Dr. Sasane has nothing to disclose. The institution of Dr. Armstrong has received research support from National Institute of Aging. The institution of Dr. Armstrong has received research support from Florida Department of Health. The institution of Dr. Armstrong has received research support from Lewy Body Dementia Association. Dr. Armstrong has received research support from Parkinson Foundation. Dr. Armstrong has received personal compensation in the range of $5,000-$9,999 for serving as a DSMB member with Alzheimer’s Clinical Trials Consortium. Dr. Armstrong has received personal compensation in the range of $5,000-$9,999 for serving as a DSMB member with Alzheimer’s Disease Cooperative Study. Dr. Armstrong has a non-compensated relationship as a Member, Scientific Advisory Council with Lewy Body Dementia Association that is relevant to AAN interests or activities. Dr. Feuerstein has nothing to disclose. Dr. Shill has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amneal Pharmaceuticals. Dr. Shill has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurocrine Biosciences. Dr. Shill has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Shill has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbive. Dr. Talman has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Oregon Federal Public Defenders Office. Dr. Talman has received personal compensation in the range of $500-$4,999 for serving as a panelist with HDSA. Dr. Mantri has received personal compensation in the range of $0-$499 for serving as a Consultant for Deep Brain Innovations, LLC. Dr. Mantri has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Grey Matter Technology. The institution of Dr. Mantri has received research support from The Michael J Fox Foundation for Parkinson Research.

Evaluation of Khaya gum (Khaya senegalensis) as a polymer in the formulation of floating in situ gels of metoprolol succinate

Metoprolol succinate, a β-selectiveadrenergic blocker, has a short half-life, low bioavailability, and high dosingfrequency. In-situ gel drug delivery is a good approach to achieve sustained release for once-daily administration thatwill prolong drugretention time at the stomach and increase absorption. Thus,the aim of the study is to formulate floatingin-situ gel formulations of metoprolol succinate using Khaya gum (Khayasenegalensis, family Meliaceae) as a polymer. Khaya gum wascharacterized and used in formulating in situ gels of metoprololsuccinate in comparison with Hydroxyl Propyl Methyl Cellulose (HPMC K15M) andXanthan gum. The in-situ gel formulations were characterized forappearance, swelling, in- vitro buoyancy and in-vitro drugrelease. FTIR revealed major peaks characteristic of the gum. Khaya gum showedhigh swelling and good flow properties. In-situ gel formulations of metoprolol succinatecontaining Khaya were light brown with near neutral pH, higher swelling and a total floating time &amp;gt;24 h,comparable to those containing HPMC and Xanthan gums. Dissolution time t80was 60.50 to &amp;gt;240 min with ranking Khaya&amp;nbsp;&amp;lt;HPMC&amp;nbsp;&amp;lt;Xanthan. Khaya gum providesa cheaper, suitable polymer for formulating floating in-situ gels with prolonged buoyancy and drug release.

Design, Development, and Evaluation of Treprostinil Embedded Adhesive Transdermal Patch.

Clinical application of treprostinil in pulmonary arterial hypertension is hampered by adverse effects caused by its high dosing frequency. The objective of this investigation was to Formulate an adhesive-type transdermal patch of treprostinil and evaluate it both in vitro and in vivo. A 32-factorial design was utilized to optimize the selected independent variables (X1: drug amount, X2: enhancer concentration) on the response variables (Y1: drug release, Y2: transdermal flux). The optimized patch was evaluated for various pharmaceutical properties, skin irritation, and pharmacokinetics in rats. Optimization results signify considerable influence (p < 0.0001) of X1 on both Y1 and Y2, as compared to X2. The optimized patch possesses higher drug content (>95%), suitable surface morphology, and an absence of drug crystallization. FTIR analysis revealed compatibility of the drug with excipients, whereas DSC thermograms indicate that the drug exists as amorphous in the patch. The adhesive properties of the prepared patch confirm adequate adhesion and painless removal, while the skin irritation study confirms its safety. A steady drug release via Fickian diffusion and greater transdermal delivery (~23.26 µg/cm2/h) substantiate the potential of the optimized patch. Transdermal therapy resulted in higher treprostinil absorption (p < 0.0001) and relative bioavailability (237%) when compared to oral administration. Overall, the results indicate that the developed drug in the adhesive patch can effectively deliver treprostinil through the skin and could be a promising treatment option for pulmonary arterial hypertension.

Preliminary health risk assessment of two exudate gums as pharmaceutical excipients

Some exudate gums such as acacia and tragacanth gums have been certified to be used in pharmacy as excipients. In this study exudate gums, obtained from two local trees in Ghana: Cussonia arborea and Cordia mellinii, were assessed for their safety for use as pharmaceutical excipients. The crude gums were purified using water and 96% ethanol and digested by di-acid procedure using 65% HNO3 and 37% HCl (2:3) at 95 °C for elemental analysis. Quantification of Ca, Fe, Mg, Cu, Zn, Mn, Ni, Hg, Cd, Pb and As ions was done using AAS 400; Na and K using the single channel flame photometer; and P using Spectronic 20 spectrophotometer. Microbial quality of the purified gums was also determined by the British Pharmacopoeia method. Toxicity of the purified gums was evaluated using acute and sub chronic murine toxicity models. Quantities of elemental ions detected in both purified gums were not significantly high to affect the utilization of these gums as pharmaceutical excipients even in large dose and high dosing frequency drugs. Total aerobic viable counts of the gums were within the acceptable Pharmacopoeial specification and no harmful microorganisms were detected. Acute and sub-chronic toxicity tests of the gums showed that they are safe for use even in long term dosage regimen medications. Thus, when these gums are included in even long term use medicines as excipients, may not cause any harm to the patient. The gums are therefore safe and qualified for use as pharmaceutical excipients when purified.

Evaluation of Pharmacokinetics, Biodistribution, and Antimalarial Efficacy of Artemether-Loaded Polymeric Nanorods.

Artemether oily injection is recommended for the treatment of severe malaria by the intramuscular route. The major limitations of the artemisinin combination therapy are erratic absorption from the injection site and high dosing frequency due to a very short elimination half-life of the drug. Advanced drug delivery systems have shown significant improvement in the current malaria therapy; the desired drug concentration within infected erythrocytes is yet the major challenge. Recently, we have reported the fabrication of artemether-loaded polymeric nanorods for intravenous malaria therapy which was found to be biocompatible with THP-1 monocytes and rat erythrocytes. The objective of the present study was the evaluation of pharmacokinetics, biodistribution, and antimalarial efficacy of artemether-loaded polymeric nanorods. Scanning electron microscopy and confocal microscopy studies revealed that both nanospheres and nanorods were adsorbed onto the surface of rat erythrocytes after an incubation of 10 min. After intravenous administration to rats, artemether nanorods showed higher plasma concentration and lower elimination rate of artemether when compared with nanospheres. The biodistribution studies showed that, at 30 min, the liver concentration of DiR-loaded nanospheres was higher than that of DiR-loaded nanorods after intravenous administration to BALB/c mice. The in vitro schizont inhibition study showed that both nanorods and nanospheres exhibited concentration-dependent parasitic inhibition, wherein at lower concentrations (2 ppm), nanorods were more effective than nanospheres. However, at higher concentrations, nanospheres were found to be more effective. Nanorods showed higher chemosuppression on day 5 and day 7 than nanospheres and free artemether when studied with the Plasmodium berghei mouse model. Moreover, the survival rate of P. berghei infected mice was also found to be higher after treatment with artemether nanoformulations when compared with free artemether. In conclusion, polymeric nanorods could be a promising next-generation delivery system for the treatment of malaria.

Design and evaluation of rufinamide nanocrystals loaded thermoresponsive nasal in situ gelling system for improved drug distribution to brain.

Rufinamide (Rufi) is an antiepileptic drug used to manage Lennox-Gastaut Syndrome and partial seizures. The oral bioavailability of Rufi is less due to its poor solubility and low dissolution rate in the gastrointestinal fluids. This results in less amount of drug reaching the brain following the oral administration of drug. Oral formulations of Rufi are prescribed at a high dose and dosing frequency to increase its distribution to the brain. A Rufi loaded thermoresponsive nasal in situ gel which showed significantly high brain concentrations compared to aqueous suspension of Rufi administered through nasal route was developed by our research group and published. In the current work, we have formulated nanocrystals of Rufi and suspended them in a xyloglucan based thermoresponsive gel to improve the nose-to-brain distribution. The particle size, polydispersity index, and yield (%) of the optimized Rufi nanocrystals were 261.2 ± 2.1 nm, 0.28 ± 0.08, and 89.6 ± 2.0 respectively. The narrow PDI indicates that the manufacturing process is reproducible and reliable. Higher % yield suggested that the method of preparation is efficient. The sol-to-gel transition of in situ gel loaded with Rufi nanocrystals was at 32°C which suggested that the formulation transforms into gel at nasal epithelial temperatures. The nasal pharmacokinetic studies showed that Rufi nanocrystals loaded in situ gel produced higher concentration of the drug in brain (higher brain Cmax) and maintained the drug concentrations for longer duration (higher mean residence time) compared to aqueous suspension of Rufi nanocrystals as well aqueous suspension of Rufi and Rufi loaded in situ gel, reported previously. Nanometric size of the Rufi nanocrystals combined with the in situ gelling properties helped the optimized formulation achieve higher brain distribution and also sustain the drug concentrations in brain for longer duration compared to any of the formulations studied by our research group.

Exploring Therapeutic Potential of Invasomes, Transfersomes, Transethosomes, Oleic Acid Vesicles, and Cubosomes Adopting Topical/Transdermal Route

Background: Transdermal drug delivery is considered a better alternative to oral administration of drugs like proteins or peptides that are susceptible to extensive degradation via first pass metabolism. This delivery route also shows high patient compliance due to no use of painful injections. Conventional delivery systems like creams and gel show poor skin permeation and high dosing frequency. Objective: The objective of this work was to investigate the role of highly advanced micro and nanocarrier systems like invasomes, transfersomes, transethosomes, oleic acid vesicles, and cubosomes for transdermal drug delivery exploring literature survey. Methods: Literature survey for these advanced micro and nanocarrier systems was carried out using search engines like Pubmed and Google scholar. Results: Results of literature investigations revealed that advanced micro and nanocarrier systems discussed earlier have the caliber to enhance skin permeation of various bioactives, show sustain release, and target particular areas of skin better compared to old nanocarriers like liposomes. Conclusion: The present review concludes that advanced micro and nanocarrier systems like invasomes, transfersomes, transethosomes, oleic acid vesicles, and cubosomes are better alternatives for transdermal delivery of therapeutic agents compared to old nanocarriers like liposomes and conventional delivery systems like creams and gels.

A Review on Pharmacological and Therapeutical Insight of Satranidazole for Colon Targeting in the treatment of Colonic Diseases

Drugs targeting the colonic environment to treat various colonic diseases are the major challenges recently. Various drugs are available in the markets to targeting to the colonic region to treat diseases but due to premature drug releases, target specificity, the low concentration at the target site with high adverse effects which increase patients’ compliance day by day. Satranidazole is a promising drug that is particularly targeting the colonic environment and can break down microorganism DNA to involve the treatment of several diseases such as inflammatory bowel diseases subdivided Ulcerative colitis, Crohn’s disease, amoebiasis, chronic diarrhea, and reduction of pain due to inflammation. Conventional drug delivery of Satranidazole has some disadvantages such as target specificity, high dosing frequency, low therapeutic efficacy, and high adverse effects that can be overcome through targeted drug delivery systems. Satranidazole is successfully showing the efficacy against aerobic, microaerophilic as well as anaerobic bacterial and reduction of inflammation of inflammatory bowel diseases subdivided as Ulcerative colitis and Crohn’s disease. It is a much more potent drug than metronidazole and has fewer adverse effects. Satranidazole is more convenient for oral administration compared to other routes of administration to show activity. Researchers are giving much more attention to targeted drug delivery systems of Satranidazole to show high therapeutic activity with fewer side effects. The current review focus on the pharmacological and therapeutical insight of Satranidazole in the treatment of colonic diseases and recent advancement and the future aspects of Satranidazole targeting various diseases. &#x0D; Keywords: Satranidazole, Inflammatory bowel diseases, Ulcerative colitis, Crohn’s disease, Amoebiasis, Targeted drug delivery system, Future advancement, Colonic drug delivery systems.

Application of Lipid-Based Nanocarriers for Antitubercular Drug Delivery: A Review.

The antimicrobial drugs currently used for the management of tuberculosis (TB) exhibit poor bioavailability that necessitates prolonged treatment regimens and high dosing frequency to achieve optimal therapeutic outcomes. In addition, these agents cause severe adverse effects, as well as having detrimental interactions with other drugs used in the treatment of comorbid conditions such as HIV/AIDS. The challenges associated with the current TB regimens contribute to low levels of patient adherence and, consequently, the development of multidrug-resistant TB strains. This has led to the urgent need to develop newer drug delivery systems to improve the treatment of TB. Targeted drug delivery systems provide higher drug concentrations at the infection site, thus leading to reduced incidences of adverse effects. Lipid-based nanocarriers have proven to be effective in improving the solubility and bioavailability of antimicrobials whilst decreasing the incidence of adverse effects through targeted delivery. The potential application of lipid-based carriers such as liposomes, niosomes, solid lipid nanoparticles, nanostructured lipid carriers, nano and microemulsions, and self-emulsifying drug delivery systems for the treatment of TB is reviewed herein. The composition of the investigated lipid-based carriers, their characteristics, and their influence on bioavailability, toxicity, and sustained drug delivery are also discussed. Overall, lipid-based systems have shown great promise in anti-TB drug delivery applications. The summary of the reviewed data encourages future efforts to boost the translational development of lipid-based nanocarriers to improve TB therapy.