Optimization of the Preparation of Nalmefene-Loaded Sustained-Release Microspheres Using Central Composite Design

Abstract

Nalmefene is a m selective opioid antagonist which is similar to naloxone in structure and pharmacology. Receptor binding studies have shown that nalmefene, like naloxone and the other opioid antagonist naltrexone, had high affinity for m, k and d receptors, furthermore, it bound more tightly with these receptors than naltrexone. [1][2][3] In animal models, nalmefene has many properties of opioid antagonist which have been demonstrated under a wide range of conditions. Studies on humans have also demonstrated opioid antagonist effects of nalmefene. 4) In addition to the reversal of opioid agonist effects, nalmefene provides an alternative to methadone for the treatment of opioid dependence. 1,4,5) Nalmefene has specific pharmacological properties which may make it more useful than other opioid antagonists as an abstinence treatment for opioid dependence. 4,6) The number of narcotics-abusers in China is quite staggering. According to statistics of government, heroin-abusers are estimated to be 0.791 million. Many relevant medical agencies had made continuous efforts to reduce the population of narcoticabusers, but seldom achieved the ideal goal. Statistics showed that 98.2% subjects who entered those treatment programs had a dismal record of relapse, and only a small proportion remained clean long after the program. The disease caused by narcotics abuse remains a scourge of society. It becomes an increasingly important task for us to help addicted individuals to get rid of their dependency or at least decrease the level of dependency to make them be a functional member of society.The relapse of addiction is often caused by the compliance and lack of retention. 5,7-9) A repetitive treatment act, such as asking subjects to take a pill daily, is not easy thing, even they have no doubt of taking the pill. When the narcoticsabuser has physiological and emotional needs for the abused substance, the therapeutic routine becomes more difficult. The lack of perseverance of the subject decreases the chance of success of the treatment. Therefore, it is of great importance to be able to reduce the level of involvement of the subject during medicinal treatments, particularly those treatments involving a particular regimen.Many experts adopt sustained-release method to reduce the involvement of compliance. Various slow-release biodegradable microspheres have been developed for a variety of drugs, and some of them are commercialized. Among various biodegradable polymers, the poly(lactic-co-glycolic acid) (PLGA) is the most widely studied and used.10-12) The properties of the microspheres are sensitive to many variableness of preparation and condition of the preparing and selecting process. In this study, we have studied the effect of formulation variables of sustained release microspheres on several response variables, and subsequently, we have utilized response surface methodology to optimize the formulation after constructing a desirable function that combines three response variables. ExperimentalMaterials and Apparatus PLGA ...

Sustained release biodegradable solid lipid microparticles: Formulation, evaluation and statistical optimization by response surface methodology

“…The effect of different controlled independent factors on different responses/features of a formulation can be studied effectively with the help of Central composite Rotatable Design (CCRD), which is a statistical procedure for optimization of formulations and is usually employed using software like Design Expert (version 8.0.6.1 Stat-ease, Inc.). CCRD also suggests a model equation for a specific response as a function of various controlled independent variables (17)(18).…”

“…The level of significance was set at 0.05. Two dimensional contour and 3D surface plots were plotted to assess the effects of independent variables on dependent variables (17)(18). Comparison was also made between experimental and predicted values.…”

Design, Optimization and in Vitro Characterization of Self Nano Emulsifying Drug Delivery System of Olmesartan Medoxomil

“…3 (a-c). As these types of plots can only express two independent variables at a time against the response, one independent variable must always be fixed [30].…”

Anti-Infectious Activity of Intravitreal Injectable Voriconazole Microspheres on Experimental Rabbit Fungal Endophthalmitis Caused by aspergillus fumigatus

“…21 In brief, about 5 mg of microspheres was weighted and added to a dialysis bag (MD34; Solarbio, Marseille, France) with a Mw cutoff of 8-14 kDa, and 5 mL phosphate buffered saline (PBS, 0.01 M, pH 7.4, containing 0.02% NaN 3 ) was then added. The dialysis bag containing the microsphere suspension was kept in a beaker of 45 mL PBS as the release medium and shaken at a rate of 72 r/min at 37 • C. A volume of 1.0 mL of medium was drawn out at the predetermined daily interval and the same volume of fresh PBS was replenished.…”