Long-term study of ropinirole patch in Parkinson's disease patients with/without basal l-dopa

IntroductionA dopamine agonist patch could be an important treatment option for Parkinson's disease. This study evaluated the long-term efficacy and safety of the ropinirole hydrochloride patch. The steady state plasma ropinirole concentration was also assessed.MethodsIn a multicenter, open-label, uncontrolled study, Parkinson's disease patients with/without basal levodopa and with/without prior dopamine agonist therapy (any of these four regimens) received application of a ropinirole patch once daily for up to 52 weeks with unforced titration from 8 to 64 mg. For patients with prior dopamine agonist therapy, the initial dose of ropinirole patch was determined from the prior dopamine agonist dose by using a conversion table.ResultsMost adverse events were mild or moderate. All application site adverse events were mild, except for moderate application site erythema in one patient. In patients with prior dopamine agonist therapy, switching to ropinirole patch did not lead to a significant early increase of adverse events. A change from baseline in the UPDRS Part III total score, the primary efficacy endpoint, showed improvement until Week 16 compared with baseline, followed by little subsequent change until Week 52, indicating maintenance of efficacy. The plasma ropinirole concentration was at steady state throughout the study period and showed a dose-proportional increase.ConclusionOnce-daily application of ropinirole patch showed long-term efficacy and safety (52 weeks) for Parkinson's disease. Switching from other dopamine agonists to ropinirole patch was effective and safe. The plasma ropinirole concentration was at steady state throughout the study period and showed a dose-proportional increase.     

Aqueous solubility: Simple predictive methods (in silico,in vitro and bio-relevant approaches)

Aqueous solubility is a key physicochemical attribute required for the characterisation of an active pharmaceutical ingredient (API) during drug discovery and beyond. Furthermore, aqueous solubility is highly important for formulation selection and subsequent development processes. This review provides a summary of simple predictive methods used to assess aqueous solubility as well as an assessment of the more complex in silico methodologies and a review of the recent solubility challenge. In addition, a summary of experimental methods to determine solubility is included, with a discussion of some potential pitfalls.     

Some Preformulation Studies of Pyruvic Acid and Other α-Keto Carboxylic Acids in Aqueous Solution: Pharmaceutical Formulation Implications for These Peroxide Scavengers

The purpose of this study is to assess some of the variables determining the aldol-like condensation of pyruvic acid (1), a peroxide scavenger, in aqueous solution to parapyruvic acid and higher oligomers. Its stability is compared to 3 other α-keto carboxylic acids, 2 with sterically hindered methylene groups alpha to the keto functionality (2-3) and phenylglyoxylic acid (4) with no methylene group. High-performance liquid chromatography, nuclear magnetic resonance, and liquid chromatography mass spectroscopy techniques are used in the kinetics and product analyses. 1 condensation is concentration dependent and base catalyzed above pH 7, consistent with the reaction mechanism proceeding through the attack of the fraction of the methylene group, alpha to the keto group, in its anionic form, at the keto group of a second molecule of 1. The major product is confirmed to be parapyruvic acid, but higher-order oligomers are also observed. All 3 of the other α-keto carboxylic acids 2-4 are considerably less reactive, with 4 being completely stable. Stable solutions of 1 can be prepared by the use of relatively dilute solutions maintained at slightly acidic pH values. 1 prevents the oxidation of methionine on addition of hydrogen peroxide.     

Skin permeation behavior of elastic liposomes: role of formulation ingredients

Introduction: With the incorporation of edge activators into the lipid bilayer structure, elasticity properties are given to liposomes. Regardless of the debate over the precise permeation mechanism of elastic liposomes, these vesicles have been proven to enhance drug permeation into or through skin in most cases.

Areas covered: This article provides an overview of the formulation ingredients of elastic liposomes and their relationship with skin permeation behavior. The ingredients are divided into two categories of basic and optional ingredients. The effect of stability on permeation behavior of the vesicles is highlighted.

Expert opinion: More attention should be paid to the stability of elastic liposomes. The different stability properties of the elastic liposomes following administration can induce different skin permeation behaviors of the vesicles. It is necessary to select the optimum composition of the elastic liposomes in order to control the stability and permeation behavior of the vesicles into or through the skin. Moreover, for the development of elastic liposomes, particular attention should also be paid to the drug leakage from the vesicles during long-term storage. The application of optional ingredients to improve the stability and/or elasticity of the elastic liposomes is becoming a new trend.     

Ultrasonic resonator technology as a new quality control method evaluating gelatin nanoparticles

Nanomedicine is a quickly evolving field where more and more possible applications become evident and start entering clinical trials or even the market. However, the analytic methods are not always able to keep pace with the new formulations’ demands. One example of a promising medical implementation is oligodeoxynucleotide (ODN) delivery by gelatin nanoparticles (GNPs). Currently, quality control is dependent on either some time consuming or destructive spectrometric, chromatographic or electrophoretic methods. A possible enlargement of the portfolio by Ultrasonic Resonator Technology (URT) is investigated here by subjecting plain GNPs in various sizes and concentrations as well as ODN-loaded GNPs to URT analysis. If calibrated by photon correlation spectroscopy (PCS) and other spectroscopy methods for each single nanoparticle system parameter, URT is an efficient and non-destructive technique and serves as a broad characterization method. URT is emphasized to play a possible future part in the size, concentration and ODN loading monitoring, e.g. of gelatin nanoparticles in the course of formulation development.     

Aerosol particle generation from solution-based pressurized metered dose inhalers: a technical overview of parameters that influence respiratory deposition

Abstract

There are a multitude of formulation factors to consider when developing a solution-based pressurized metered dose inhaler (pMDI). Evaluation of these variables and their underpinning driving force has been performed over the years. Key components, including formulation composition and device design, play significant roles in determining the aerosol performance of these solution-based formulations. This review outlines research efforts that have focused on these essential governing factors, how the aerosol performance changes when these variables are modified and fundamental mechanisms affecting the delivery efficiency of such formulations.     

A new self-emulsifying formulation of mefenamic acid with enhanced drug dissolution

To enhance the dissolution of poorly soluble mefenamic acid, self-emulsifying formulation (SEF), composing of oil, surfactant and co-surfactant, was formulated. Among the oils and surfactants studied, Imwitor^® 742, Tween^® 60, Cremophore^® EL and Transcutol^® HP were selected as they showed maximal solubility to mefenamic acid. The ternary phase diagram was constructed to find optimal concentration that provided the highest drug loading. The droplet size after dispersion and drug dissolution of selected formulations were investigated. The results showed that the formulation containing Imwitor^® 742, Tween^® 60 and Transcutol^® HP (10:30:60) can encapsulate high amount of mefenamic acid. The dissolution study demonstrated that, in the medium containing surfactant, nearly 100% of mefenamic acid were dissolved from SEF within 5 min while 80% of drugs were dissolved from the commercial product in 45 min. In phosphate buffer (without surfactant), 80% of drug were dissolved from the developed SEF within 5 min while only about 13% of drug were dissolved in 45 min, from the commercial product. The results suggested that the SEF can enhance the dissolution of poorly soluble drug and has a potential to enhance drug absorption and improve bioavailability of drug.