The attitude of patients with progressive ataxias towards clinical trials

Background The development of new therapies may rely on the conduct of human experimentation as well as later clinical trials of therapeutic interventions. Ethical considerations seek to protect the patient from risk but few have sought to ascertain the attitude to such risk of patients with progressive debilitating or terminal conditions, for which no mitigating or curative therapies exist. Such understanding is also important if recruitment is to be maximized. We therefore sought to define the motivations for and barriers to trial participation amongst patients with progressive ataxias, as well as their condition-specific trial preferences. Methods We conducted an online survey consisting of 29 questions covering four key domains (demographics, personal motivation, drug therapy and study design) relating to the design of clinical trials. Two major ataxia charities, Ataxia UK and the Friedreich’s Ataxia Research Alliance (FARA) sent the survey to their members. Responses were analysed by disease and by ambulatory status. Results Of 342 respondents, 204 reported a diagnosis of Friedreich’s ataxia (FRDA), 55 inherited cerebellar ataxia (CA) and 70 idiopathic CA. The most important symptoms to be addressed by a trial were considered to be balance problems and ambulation, although these were superseded by speech problems in wheelchair users. Common motivations for participation were potential benefits to self and others. Reasons for non-participation included concerns about side effects, and the burden and cost of travel. Financial reimbursement for expenses was reported to be likely to increase trial engagement, Phase two trials were the most popular to participate in, and the use of a placebo arm was seen as a disincentive. Across all disease subgroups, drug repurposing trials proved popular and just under 70% of participants would be prepared to undergo intrathecal drug administration. Conclusions Knowledge of motivations for and barriers to trial participation as well as the acceptability of investigations, time commitments and routes of drug administration should inform better, more patient focused trial design. This in turn may improve recruitment and retention of participants to future trials.

Stimuli-Responsive Polymers for Transdermal, Transmucosal and Ocular Drug Delivery

Despite their conventional and widespread use, oral and intravenous routes of drug administration face several limitations. In particular, orally administered drugs undergo enzymatic degradation in the gastrointestinal tract and first-pass metabolism in the liver, which tend to decrease their bioavailability. Intravenous infusions of medications are invasive, painful and stressful for patients and carry the risk of infections, tissue damage and other adverse reactions. In order to account for these disadvantages, alternative routes of drug delivery, such as transdermal, nasal, oromucosal, ocular and others, have been considered. Moreover, drug formulations have been modified in order to improve their storage stability, solubility, absorption and safety. Recently, stimuli-responsive polymers have been shown to achieve controlled release and enhance the bioavailability of multiple drugs. In this review, we discuss the most up-to-date use of stimuli-responsive materials in order to optimize the delivery of medications that are unstable to pH or undergo primary metabolism via transdermal, nasal, oromucosal and ocular routes. Release kinetics, diffusion parameters and permeation rate of the drug via the mucosa or skin are discussed as well.

Forty Years of Evidence on the Efficacy and Safety of Oral and Injectable Antibiotics for Treating Lyme Disease of Adults and Children: A Network Meta-Analysis

Some previous studies investigated the efficacy and safety of antibiotics for treating Lyme disease (LD). However, due to technical limitations, several questions regarding the routes of drug administration and the dosages of drug are still unclear, which might be causing problems for clinicians.

FORMULATION AND EVALUATION OF ANTIFUNGAL CREAM OF CHLORPHENESIN

Objective: The main aim of our research was to develop an Antifungal cream formulation consisting of Chlorphenesin for the treatment of Fungal infections. Topical route is the most suitable route for skin infections. Methods: The development of topical drug delivery systems designed to have systemic effects appears to be beneficial for a number of drugs on account of several advantages over conventional dosage forms(or) routes of drug administration. An Antifungal cream formulation consisting of Chlorphenesin was prepared. Results: The formulation was subjected to in vitro diffusion studies. Microbiological studies were performed to find out the safety of materials used in the formulation. Conclusion: The developed cream consisting of Cholrphnesin was found to be safe and effective for the treatment of fungal infection.

Brain Metabolic Profile after Intranasal vs. Intraperitoneal Clomipramine Treatment in Rats with Ultrasound Model of Depression

Background: Molecular mechanisms of depression remain unclear. The brain metabolome after antidepressant therapy is poorly understood and had not been performed for different routes of drug administration before the present study. Rats were exposed to chronic ultrasound stress and treated with intranasal and intraperitoneal clomipramine. We then analyzed 28 metabolites in the frontal cortex and hippocampus. Methods: Rats’ behavior was identified in such tests: social interaction, sucrose preference, forced swim, and Morris water maze. Metabolic analysis was performed with liquid chromatography. Results: After ultrasound stress pronounced depressive-like behavior, clomipramine had an equally antidepressant effect after intranasal and intraperitoneal administration on behavior. Ultrasound stress contributed to changes of the metabolomic pathways associated with pathophysiology of depression. Clomipramine affected global metabolome in frontal cortex and hippocampus in a different way that depended on the route of administration. Intranasal route was associated with more significant changes of metabolites composition in the frontal cortex compared to the control and ultrasound groups while the intraperitoneal route corresponded with more profound changes in hippocampal metabolome compared to other groups. Since far metabolic processes in the brain can change in many ways depending on different routes of administration, the antidepressant therapy should also be evaluated from this point of view.

Orodispersible Tablet in Treatment of Migraine: Opportunities, Challenges and Recent Advancements

The most comfortable and choicely path of drug administration is oral route. Orodispersible tablets bring a revolution among all routes of drug administration as well as oral route of drug administration also. Orodispersible tablets are unit dosage form but it has unique characteristics. It disintegrates in the mouth within a minute for the presence of saliva where the presence of super disintegrates in the preparation. Especially, old and child have no chance to swallow as a result it is very acceptable for them. Migraine is a very well-known irritating condition for adult and female. Migraine is a debilitating and common neurovascular illness associated with symptoms of one-sided headache, nausea with or without vomiting, photophobia and/or phonophobia. But these symptoms are subjective and vary from patient to patient. Orodispersible tablets are most important solution of migraine like emergency condition and helping human by transferring from hell to heaven. Very short half-life, quick disintegration, quick onset of action and better bioavailability brings the orodispersible tablets into the top position of the management of migraine. Sumatriptan, zolmitriptan like drugs are helping their hands to reduce migraine. Lastly, there are lots of drugs are investigating for this purpose and our hope that the orodispersible tablet can give the pioneer and will give the migraine free era to us and our futures. Keywords: Orodispersible tablet, migraine, sumatriptan, super disintegrate, fast dissolving

The Attitude of Patients with Progressive Ataxias Towards Clinical Trials

Background: The development of new therapies may rely on the conduct of human experimentation as well as later clinical trials of therapeutic interventions. Ethical considerations seek to protect the patient from risk but few have sought to ascertain the attitude to such risk of patients with progressive debilitating or terminal conditions, for which no mitigating or curative therapies exist. Such understanding is also important if recruitment is to be maximized. We therefore sought to define the motivations for and barriers to trial participation amongst patients with progressive ataxias, as well as their condition-specific trial preferences. Methods: We conducted an online survey consisting of 29 questions covering four key domains (demographics, personal motivation, drug therapy and study design) relating to the design of clinical trials. Two major ataxia charities, Ataxia UK and the Friedreich’s Ataxia Research Alliance (FARA) sent the survey to their members. Responses were analysed by disease and by ambulatory status.Results: Of 342 respondents, 204 reported a diagnosis of Friedreich’s ataxia (FRDA), 55 inherited cerebellar ataxia (CA) and 70 idiopathic CA. The most important symptoms to be addressed by a trial were considered to be balance problems and ambulation, although these were superseded by speech problems in wheelchair users. Common motivations for participation were potential benefits to self and others. Reasons for non-participation included concerns about side effects, and the burden and cost of travel. Financial reimbursement for expenses was reported to be likely to increase trial engagement, Phase two trials were the most popular to participate in, and the use of a placebo arm was seen as a disincentive. Across all disease subgroups, drug repurposing trials proved popular and just under 70% of participants would be prepared to undergo intrathecal drug administration.Conclusions: Knowledge of motivations for and barriers to trial participation as well as the acceptability of investigations, time commitments and routes of drug administration should inform better, more patient focused trial design. This in turn may improve recruitment and retention of participants to future trials.

Liposomes and transferosomes: a breakthrough in topical and transdermal delivery

The topical and transdermal routes of drug administration are long known to the field of pharmaceutics. These routes have been explored for the delivery of a wide range of therapeutic agents over centuries. However, the anatomy of the skin and the physicochemical properties of molecules limit their transport via these routes. To overcome these challenges, a nano-phospholipid carrier called liposome was developed in the 1960s. Liposomal delivery of drugs was reported to be limited to the upper layers of skin. This led to the development of self-regulating and self-adaptable vesicles known as transfersomes. This review critically evaluates the barriers in delivery across the skin, recent advancements in liposomes, transfersomes and their impact in the pharmaceutical field.

Pharmacodynamic evaluation of Dezocine injection from Yangtze River Pharmaceutical Group

Intramuscular injection and intravenous injection are important routes of drug administration, which not only have a fast absorption rate, but also avoid the first pass effect of the drug. In 2009, Yangtze Pharmaceutical Group redeveloped Dezocine(13-Amino-5,6,7,8,9,10,11,12-octahydro-5-methyl-5,11-methanobenzocyclodecen-3-ol), molecular formula: C16H23NO, in the form of njection. Quickly, Dezocine injection becomes the first choice for perioperative pain management in China and accounts for 45 % of the analgesic market. This study mainly used animal pain models to study the analgesic effects of Dezocine injection. The results indicated that Dezocine produced potent analgesic effect in the hot plate and writhing tests.

Road From Nose to Brain for Treatment of Alzheimer: The Bumps and Humps

: Vulnerability of the brain milieu to even the subtle changes in its normal physiology is guarded by a highly efficient blood brain barrier. A number of factors i.e. molecular weight of the drug, its route of administration, lipophilic character etc. play a significant role in its sojourn through the blood brain barrier (BBB) and limit the movement of drug into brain tissue through BBB. To overcome these problems, alternative routes of drug administration have been explored to target the drugs to brain tissue. Nasal route has been widely reported for the administration of drugs for treatment of Alzheimer. In this innovative approach, the challenge of BBB is bypassed. Through this route, both the larger as well as polar molecules can be made to reach the brain tissues. Generally, these systems are either pH dependent or temperature dependent. Results: The present review highlights the anatomy of nose, mechanisms of drug delivery from nose to brain, critical factors in the formulation of nasal drug delivery system, nasal formulations of various drugs that have been tried for their nasal delivery for treatment of Alzheimer. Conclusion: It also dives deep to understand the factors that contribute to the success of such formulations to carve out a direction for this niche area to be explored further.