Us20090298847a1 manufacturing method of solid dispersion. Carrier selection in solid dispersion is a difficult process. The drug can be dispersed molecularly, in amorphous particles clusters or in. Characterization of solid dispersion of itraconazole prepared. Physical stabilization of amorphous itraconazole in solid.
In this paper, pcz hot melt extruded amorphous solid dispersion sd with. Preparation and characterization of quercetinpolyvinylpyrrolidone k. Amphotericin b colloidal dispersion abcd, amphocil 2 mgkgday for. Solid dispersion of paracetamol was prepared with dissolving paracetamol with weighed quantity of methanol, the solution was stirred for 3 hrs to make transparent solution of dispersion phase, the prepared solution than slowly dispersed on the solid material with continuous triturating to ensure proper mixing of dispersion solution, finally the mixture is allowed to dry at 60c for 8 hrs in. The mix was then thoroughly mixed to obtain an even dispersion of the solid dispersion on the adsorbent and then quench cooled by placing the mixture into a freezing mixture made with ice and salt. The operation was carried out using nozzle size of 0. Solid molecular dispersions of itraconazole for enhanced dissolution and controlled drug delivery liu hong, master of science 2009 graduate department of pharmaceutical sciences, university of toronto the purpose of this study was to investigate the formation of solid molecular dispersions. Investigation of itraconazole ternary amorphous solid. Srivastava1, hemesh singh1, narendra singh1 faculty of pharmacy and biotechnology, raja balwant singh engineering technical campus, bichpuri, agra corresponding author mr. Itraconazole solid dispersion prepared by a supercritical fluid technique. A solidstate approach to enable compounds in preclinical development is used by identifying an amorphous solid dispersion in a simple formulation to increase bioavailability. Solid dispersion refers to a group of solid products consisting of at least two different components, generally a hydrophilic matrix and a hydrophobic drug 3.
Solid dispersion a approach to enhance the dissolution. Enhanced solubility and dissolution rate of itraconazole by a. Handbook of pharmaceutical manufacturing formulations semisolid products volume 4 sarfaraz k. Dissolution enhancement of aceclofenac tablet by solid. A pilot analysis of morphometric assessment of itraconazole brands. Problems of solid dispersion involves formulation of solid dispersion into dosage forms is not easy the physical and chemical stability of drugs. Different ratios % ww ratio of drug and carriers i. In the current research indomethacin solid dispersions are prepared and evaluated for better solubility and bioavailability. Barghi, 4 1 aerosol research laboratory, department of pharmaceutics, school of pharmacy, tehran university of medical sciences, tehran, iran aerosol research. Hot melt extruded amorphous solid dispersion of posaconazole. It can be prepared by fusion, coprecipitation and kneading methods.
Design and optimization of itraconazole tablet employing. Solid dispersion a approach to enhance the dissolution rate. Contents parti regulatory and manufacturing guidance. Solid dispersion 2 solid dispersion is defined as dispersion of one or more active ingredients hydrophobic in an inert carrier hydrophillic at solid state prepared by melting fusion, solvent, melting solvent method. Aqueous solubility of itz in concentrated solutions of weak organic acids, such as glutaric, tartaric.
Aug 26, 2015 solid dispersion has emerged as a method of choice and has been extensively investigated to ascertain the in vivo improved performance of many drug formulations. Hence, solubility of binary solid dispersion was more compared to physical mixture. Pdf solid state concerns during drug discovery and. To overcome such problems, solid dispersion systems. The extent of increase in solubility was greater for the phdependent polymers, aea and eudragit e 100 range, 141. Solid dispersion is an efficient mean of improving the drug solubility and from last many years it withstands with the objectives of producing improved dissolution rate and. In addition, immediate release pellets containing fm or fm solid dispersion systems will be formulated so as to study the impact of solid dispersions on the in vitro dissolution rate of the drug from the pellets. Solid dispersion solid dispersion, a concept firstly introduced by sekiguchi and obi8. Drugdrug solid dispersion is a unique approach to present a poorly soluble drug in an extremely fine state of subdivision to the gastro intestinal fluids. The addition of itraconazole with polymer blend of peg and hpmc was effective with respect to the concentration of drug polymer ratio. Moreover, it was possible to obtain the rapidly disintegrating tablets with very satisfactory properties, i. Formulation of solid dispersion of the drug has attracted considerable interest as. Solid dispersions is an efficient means of improving the dissolution rate and hence the bioavailability of a range of poorly soluble drugs.
The feds beige book report suggested the economys momentumwas solid. The present invention also discloses amorphous solid dispersions obtained by the method. To prepare and characterize quercetin solid dispersion using polyvinylpyrrolidone pvp k30. Spray drying is widely used technique in developing free flowing. Solid dispersion sd is defined as the dispersion of one or more active ingredients in an inert hydrophilic carrier or matrix in a solid state, prepared by melting, using solvents or by a solventmelting method chiou, riegelman, 1971.
The purpose of this study was to develop an amorphous solid dispersion sd of an extremely waterinsoluble and very weakly basic drug, itraconazole itz, by interaction with weak organic acids and then drying that would enhance dissolution rate of drug and physical stability of formulation. The remaining portion of this article is focused on various formulations which are marketed by solid dispersion technology. Formulation of immediate release pellets containing. The study was aimed to formulate solid dispersion tablet of terbinafine hydrochloride by using carriers polyethylene glycol 6000 by melting method and polyvinyl pyrrolidone k 30 by solvent method in the drug carrier ratio of 1. Characteristics of skin deposition of itraconazole solubilized. Formulation and evaluation of fast dissolving tablet. Solid dispersions have attracted considerable interest as an efficient means of improving the dissolution rate and hence the bioavailability of a range of hydrophobic drugs. Solid dispersion has emerged as a method of choice and has been extensively investigated to ascertain the in vivo improved performance of many drug formulations. Introduction oral drug delivery is the simplest and easiest way of administering drugs, because of the greater stability, smaller bulk, accurate dosage and easy production. Preparation and characterization of various solid dispersion formulations of itraconazole to enhance the drug dissolution profile k. Amorphous solid dispersions theory and practice navnit shah. The characteristic of solid dispersion depends upon process used, type of carrier, drug and carrier ratio, type of interaction, degree of interaction between drug and carrier, composition of solvent, process conditions such as temperature, humidity and rate of cooling. Solid dispersion is molecular dispersion of drug in a polymer matrix which leads to improved solubility and hence better bioavailability. An approach to enhance the bioavailability of poorly watersoluble drugs international journal of pharmacology and pharmaceutical technology ijppt, issn.
The finished product was then stored in an airtight container in a dark and cool place for further testing. Use of solid dispersions to increase stability of dithranol. Solid molecular dispersions of itraconazole for enhanced dissolution and controlled drug delivery. To accommodate the lack of biological replicates, we instead calculated dispersion values using data from 3027 genes from among the 3119 that. Solid dispersion also termed as coprecipitates and melts. It generally involves dispersion of drug in amorphous particles clusters or in crystalline particles. Solid dispersion can form either a eutectic mixture or solid solution or glass solution. Niazi crc press boca raton london new york washington, d. Solid dispersion sd is a dosage form that is capable of increasing the solubility of the incorporated antifungal drug 10. Solid dispersion is defined as a dispersion of one or more active ingredients in an inert carrier or matrix of solid state prepared by melting fusion, solvent or melting solvent method. A solid state approach to enable compounds in preclinical development is used by identifying an amorphous solid dispersion in a simple formulation to increase bioavailability. Solid dispersions of itraconazole prepared with the phindependent and dependent hydrophilic polymers all showed increased drug solubility over the pure material. Invasive antifungal infections are reasons for morbidity and mortality in immunogenic patients worldwide.
Vhvpqpykvgdnfyzpgvkddisan itraconazole chemical compound. They can be used to increase the solubility of a drug with low aqueous solubility, thereby improving its oral bioavailability. The itraconazolecontaining solid dispersion of the present invention is also. The oil also serve as a carrier for additives and or a safner. In this paper, pcz hot melt extruded amorphous solid dispersion sd. In the present paper we discuss the preparation of icz loaded solid dispersions, characterization and. Preparation, characterization and dissolution of solid. Manufacturing method of solid dispersion containing itraconazole download pdf. Spray drying is widely used technique in developing free flowing powders from aqueous or non aqueous suspensions and solutions9. Enhanced solubility and dissolution rate of itraconazole. The product formed contains different components i. Continuous production of itraconazolebased solid dispersions.
Preparation and characterization of various solid dispersion. The ow creams consist of oil droplets dispersed in water, and. It is relevant to classify various systems of solid dispersion as per as their fast release mechanisms are concerned. Wo2016016665a1 a method of preparing amorphous solid. Characterization of solid dispersion of itraconazole. Solid dispersion can be defined as a dispersion of one or more active ingredients in an inert carrier or matrix in the solid state prepared by the melt, solvent or solventmelt method. To make a solid oral dosage form, the prepared solid dispersions shall have suitable flow property.
Preparation of rapidly disintegrating tablets containing. Chiou and riegalman defined the term solid dispersion as a dispersion involving the formulation of eutectic. Preparation of itraconazole solid dispersion the solid dispersion was prepared by spray drying technique employing labultima lu 222 advanced spray dryer labultima, mumbai, india. The solubility of binary solid dispersion was found to be 0. Itraconazole solid dispersion prepared by a supercritical. Approach of solid dispersion and polymer coating in formulation of rapid dispersible tablets of paracetamol chinmay anand 1, gali vidyasagar 2 and manisha rajmane 3. Applications of solid dispersions bindu yadav 1 and y. The term solid dispersions refers to the dispersion of one or more active ingredients in an inert carrier in a solid state, frequently prepared by the melting fusion method, solvent method or fusion solventmethod. This indicates that the new ternary solid dispersion composition developed in this study demonstrates excellent physical stability upon storage and can inhibit the recrystallization of itz more. Evaluation of the solid dispersion system engineered from. Spraydried amorphous solid dispersions of griseofulvin in. Solid dispersion a novel approach for enhancement of. The drug content of binary solid dispersion was found to be 98. The purpose of this study was to investigate the formation of solid molecular dispersions of itraconazole itz in a number of glassy polymers including pvp, crospovidone, pvpec.
Solvent evaporation technique was employed to prepare films of different combinations of polymers, plasticizer, and a modal drug sulindac to narrow down on a few polymerplasticizersulindac combinations. Among the oral dosage form solid dosage forms have many advantages over other types of oral dosage forms. Solid dispersion a novel approach for enhancement of bioavailability of poorly soluble drugs in oral drug. Chapter 1 changes to approved new drug applications or abbreviated new drug applications 3 i. Although a great research interest in solid dispersion in the past four decades, the commercial utilization is very limited. Handbook of pharmaceutical manufacturing formulations. Prepared solid dispersion was evaluated for drug physical state of the drug, drug carrier interactions, dissolution rate. Download as pdf about authors bhumika kumar department of pharmaceutics, delhi pharmaceutical sciences and research university, new delhi, india abstract solid dispersion is an effective way of improving the dissolution rate of poorly water soluble drugs and hence its bioavailability.
Amorphous solid dispersion technique for improved drug. Mesoporous silica as a carrier for amorphous solid dispersion. Formulation, characterisation, permeability and genomic evaluation muhammad sheraz akbar khan doctor of philosophy march 2010 poor water solubility is characterised by low dissolution rate and consequently reduced bioavailability. Comparatively, in the last decade, amorphous drugpolymer solid dispersion has evolved into a platform technology for. Although there is ample use of water soluble carriers with no intrinsic solubilizing properties.
Physicochemical characterization and dissolution studies. Preparation and characterization of itraconazole solid. Solid dispersions of drugs with a polymer can be prepared by melting, solvent, melt evaporation, melt extrusion, microwave or supercritical methods 11. Poor water solubility is one of the major problems for the various types of drugs and various approaches have been introduced for the enhancement of. Comparatively, in the last decade, amorphous drugpolymer solid dispersion has evolved into a platform technology for delivering. Approach of solid dispersion and polymer coating in. The present study aims to experiment the solid dispersion of poorly water soluble drug itraconazole as model drug by spray drying method with the use of peghpmc polymer blends, the influence of polymer compatibility on the degree of molecular dispersion of itraconazole solid dispersions are prepared by ternary mixing and polymer blends. The solid dispersion approach has been widely and successfully applied to improve the solubility, dissolution rate and consequently the bioavailability of poorly soluble drugs. Riegelman and chiou classified solid dispersions into. Pdf during drug discovery and development the thermodynamics and kinetics of crystal.
The term solid dispersion refers to a group of solid products consisting of. Posaconazole is a most promising antifungal agent against all types of invasive infections with high % of cure rate. Solid dispersion, solubility enhancement, solvent evaporation technique, introduction solid dispersions sds are resulted by dispersion of drug in biologically inert matrix. Early stages of drug crystallization from amorphous solid dispersion. The water soluble carriers used in preparation of solid dispersion enhance the.
Solid dispersion rajni sharma, rupa mazumder, archana sharma and praveen verma department of pharmaceutical technology, noida institute of engineering and technology niet, greater noida india abstract solid dispersion, defined as the dispersion of one or more active ingredient in a carrier or matrix at solid state, is an. The sulindacpolymerplasticizer combination that was. Solid dispersion solid dispersions are classified by various ways, on the basis of their solid state structure as well as on the basis of carrier used. Protests in 2011 demanding reforms were dispersed by riot police, and the. Formulation and characterization of solid dispersion prepared. Solid dispersions, defined as the dispersion of one or more active pharmaceutical ingredient in a carrier at solid state and an efficient technique to improve dissolution of poorly watersoluble drugs to enhance their bioavailability. Formulation composition of drug amorphous solid dispersion asds with sodium dodecyl sulfate sds in various studies and survey of the. To improve the solubility of simvastatin sv by cocrystallization using.
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