Comparatively, in the last decade, amorphous drugpolymer solid dispersion has evolved into a platform technology for delivering. Solving solubility issues with amorphous solid dispersions. Several different approaches have been used to make amorphous solid dispersions, including hot. Solid dispersion a novel approach for enhancement of. Miscibility and molecular interactions over the past few decades, amorphous solid dispersions asds have been of great interest to pharmaceutical scientists to address bioavailability issues associated with poorly watersoluble drugs. Asds consist of an active pharmaceutical ingredient api. Glass is an amorphous solid that exhibits a glass transition. 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. Methods and polymers to increase the solubility of poorly soluble drugs ladan 1akbarpour nikghalb, gurinder singh2, gaurav singh2 and kimia fazaeli kahkeshan1 1gautam college of pharmacy, bangalore, karnataka, india. Sep 03, 2015 benefits of amorphous solid dispersions. The goal of the current study was to evaluate the impact of surfactants on the crystallization of celecoxib amorphous solid dispersions asd, suspended in aqueous media. We use a model asd, composed of a hydrophobic drug with copovidone and a nonionic surfactant, to explore formulation options that can. Hence, the concept of solid dispersion is gaining momentum.
Aug 11, 2017 the university of wisconsinmadison june land olakes conference on research and development is held every year and is recognized worldwide as a premier teaching conference for pharmaceutical scientists. Chapter 2 deals with the preparation of solidliquid dispersions with some emphais on the stabilization of such dispersions. Riegelman and chiou classified solid dispersions into. Sustainedrelease amorphous solid dispersions springerlink. It is therefore necessary to form solid dispersions of amorphous apis in polymeric matrices to improve their stability. Formulation and evaluation of solid dispersions of furosemide. Amorphous solid dispersions combine the increased solubility of an amorphous material and the improved physical stability of more stable solid forms. 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. Formulation and characterization of solid dispersion prepared. Feb 27, 2015 providing a roadmap from early to late stages of drug development, this book overviews amorphous solid dispersion technology a leading platform to deliver poorly water soluble drugs, a major hurdle in todays pharmaceutical industry. Improvement in solubility of poor watersoluble drugs by.
Amorphous solid dispersion is a technology for solubility enhancement of drugs. A solid dispersion technique has been used by various researchers who have reported encouraging results with different drugs the first drug whose rate and extent of absorption was significantly enhanced using the solid dispersion technique was sulfathiazole by. Amorphous solid disperions can be used in early animal studies and in marketed products. Thus the solid dispersion technique can be successfully used for the. Scanning electron microscopy sem is widely used in the characterization of amorphous solid dispersions. Nowadays, glassy solid or amorphous solid is considered to be the overarching concept, and glass the more special case. If the absorption in the gi tract is acceptable, these compounds are classified as bcd class ii. Until now, most research on asds has focused on immediaterelease formulations, supersaturation, and stability. Impact of polymer type and relative humidity on the longterm physical stability of amorphous solid dispersions. Simple eutectic mixtures when a mixture of a and b with composition e is cooled, a and b crystallize out simultaneously, whereas when other compositions are cooled, one of the components starts to crystallize out before the other. Electrospun amorphous solid dispersions of poorly water. When choosing a technology for the manufacture of an amorphous solid dispersion, the desired physiochemical traits of the resulting formulation must be taken into careful consideration. In spite of the challenges of solid state stability, it is continuing to garner the attention of researchers, a fact which is evident from the success of products that are majorly produced by solventbased. However it suffers from lack of physicalchemical stability.
Solids and liquids are both forms of condensed matter. The solid dispersion has become an established solubilization technology for poorly water soluble drugs. Mesoporous silica as a carrier for amorphous solid dispersion. Second generation of solid dispersion appeared as it was observed that solid dispersions, where the drug was maintained in. Precipitation inhibitors, such as polymers and surfactants, are usually used to stabilize the supersaturated solution by blocking the way of kinetic or. Mar 25, 2015 solid dispersion the term solid dispersion refers to a group of solid products consisting of at least two different components, generally a hydrophilic matrix and a hydrophobic drug.
A detailed search of web of science for amorphous drug solid dispersion. The selection of a manufacturing method for an amorphous solid dispersion requires indepth understanding of the benefits and risks of each approach. The solid dispersion was prepared and characterized and the results showed that 1. Jan 01, 2011 it is frequently reported that the percentage of drug candidates that are limited by poor solubility is increasing 1,2. The term solid dispersion refers to a group of solid products consisting of at least two different components, generally. Mar 26, 2014 solid dispersions are similar to a group of solid products consisting of at least two different components. Generally, asd is a solid of a polymerbased material involving a homogeneously dispersed active pharmaceutical ingredient api molecules in. Local structure of ion pair interaction in lapatinib.
As shown in ftir spectroscopic studies, the spectra of pure drug, furosemide and solid dispersion were similar and the peak for pure. One of the most common ways of stabilizing an amorphous form is by formulating it as amorphous solid dispersion. In recent years there has been a surge in the utilisation of amorphous solid dispersion asd technology. Discussion about brandon blass masters research project and thesis at asu. We use a model asd, composed of a hydrophobic drug with copovidone and a nonionic surfactant, to explore formulation options that can prevent. These systems consist of an amorphous active pharmaceutical ingredient stabilized by a polymer to produce a system with improved physical and solution stability. Solubility of a large number of apis is limited by their crystalline nature which results in poor solubility.
Research results from brandon blass thesis are shown and discussed in detail. 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 drug can be dispersed molecularly, in amorphous particles clusters or in crystalline particles 1. Furthermore, the lack of a unified nomenclature hampers the interpretation and classification of research data. 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. If dissolved, the api could in principle be miscible with the excipients over. Solid dispersion is molecular dispersion of drug in a polymer matrix which leads to improved solubility and hence better bioavailability. Amorphous solid dispersions are frequently prepared by spray drying. Pdf mesoporous silica as a carrier for amorphous solid. Drugexcipient behavior in polymeric amorphous solid. Neusilin polymer extrudates for the development of. Increases oral bioavailability of a drug increased dissolution rate. Helps readers understand amorphous solid dispersions and apply techniques to particular pharmaceutical systems covers physical and chemical.
Processing impact on performance of solid dispersions. The concept of solid dispersion was introduced by sekiguchi and obi 16 and it has become the preferred and most successful method to enhance the drug. Pdf characterization of amorphous solid dispersions. Pdf physicochemical characterization of amorphous solid.
The water soluble carriers used in preparation of solid dispersion enhance the dissolution rate of the poorly water soluble drug. A solid dispersion generally composed of two components the drug and the polymer matrix. Chiou and riegelman 1971 define solid dispersion as group of solid products consisting of at least two different components, generally, a hydrophilic matrix and a hydrophobic drug. Research has shown that asds offer unique advantages in improving the bioavailability. Amorphous materials can include amorphous drug substance 1, amorphous solid dispersions 2, and co. Providing a roadmap from early to late stages of drug development, this book overviews amorphous solid dispersion technology a leading platform to deliver poorly water soluble drugs, a major hurdle in todays pharmaceutical industry. There are several types of solid dispersion that have been used for pharmaceutical purposes, as summarized in table 1. Some of the major polymers used pharmaceutically to prepare amorphous dispersions include polyvinyl pyrrolidone pvp, hydroxypropyl methylcellulose hpmc, hpmc phthalate, and polyethylene glycolpeg.
Consists of an amorphous active pharmaceutical ingredient api stabilized by an excipient, commonly a polymer, to produce a. In this study, local structure of ionic and noninonic interactions were studied by highenergy xray diffraction and pair distribution function pdf analysis in amorphous solid dispersions. Solid dispersions the use of solid dispersions for enhancing drug solubility has become a popular strategy in recent years because of its applicability to a wide range of drug types and dosing requirements. Solid dispersion, which was introduced in the early 1970s2, refers to a group of solid products consisting of at least two different components, generally a hydrophilic matrix and a hydrophobic drug. It generally involves dispersion of drug in amorphous particles clusters or in crystalline particles. Pdf download pharmaceutical amorphous solid dispersions pdf online. Pdf the study of amorphous solid dispersions asds is currently one of the most exciting areas in pharmaceutics.
Basics of amorphous and amorphous solid dispersions ann newman seventh street development group po box 526, lafayette, in 47902 7656504462 ann. Dissolution behavior of regorafenib amorphous solid dispersion. From the results, it was clear that solid dispersion formulation showed improved dissolution rate than pure drug and physical mixture. Quantitative characterization of crystallization in. Basics of amorphous and amorphous solid dispersions. Hme has been used to prepare solid dispersion of various apis, where polymers or lipids are used as carriers 1. The very fast solvent evaporation contributes to the amorphous state of the solid dispersion. The combination of an active pharmaceutical ingredient api with such excipients is known as amorphous solid dispersions. Solid dispersion technique has been used for a wide variety of poorly aqueous soluble drugs such as nimesulide, ketoprofen, tenoxicam, nifedipine, aceclofenac, valdecoxib using various hydrophilic carriers like polyethylene glycol, polyvinylpyrrolidone. Solving poor solubility with amorphous solid dispersions. A solid dispersion sd is defined as the dispersion of a drug compound in a carrier matrix often polymers at solid state.
It is used to improve solubility of amorphous solid dispersion. Formulation and evaluation of solid dispersions of. Amorphous solid dispersions theory and practice navnit. Feb 07, 20 the aim of this paper is to investigate the physicochemical properties of binary amorphous dispersions of poorly soluble sulfonamidepolymeric excipient prepared by ball milling. Eutectics c c first type of solid dispersion prepared 2 chiou and riegelman, 1971 2. Amorphous solid dispersions and nanocrystal technologies for poorly watersoluble drug delivery. Amorphous solid dispersions asds are being used with increasing frequency for poorly soluble pharmaceutical compounds in development. Amorphous solid dispersions as enabling formulations for. The effect of inorganic salt on disintegration of tablets. Steve davidowski about research results on amorphous solid dispersions asds of cannabidiol cbd with pvp polymer.
Pharmaceutical amorphous solid dispersions download free. Amorphous solid dispersions of sulfonamidesoluplus and. Amorphous solid dispersions asds can increase the oral bioavailability of poorly soluble drugs. Pharmaceutical amorphous solid dispersions download free epub, pdf providing a roadmap from early to late stages of drug development, this book overviews amorphous solid dispersion technology a a leading platform to deliver poorly water soluble drugs, a major. Applications of solid dispersions bindu yadav 1 and y. These poorly soluble compounds typically require enabling formulations, and this trend creates challenges for teams in discovery and development who must drive invivo exposures high for animal toxicology studies and deliver robust dosage forms for clinical evaluation. The product formed contains different components i. The solid dispersion can be collected as a dry powder that most often needs some post drying to have acceptable residual solvent levels. The sulindacpolymerplasticizer combination that was.
However, their use in drug development is comparably rare due to a lack of basic understanding of mechanisms governing drug liberation and absorption in vivo. The term solid dispersion refers to a grou p of solid products consisting of at least two differe nt components, generally a hydrophilic matrix and a hydrophobic drug. Evaluation of the solid dispersion system engineered from. It is relevant to classify various systems of solid dispersion as per as their fast release mechanisms are concerned. Frank romanski, it is important to understand that solid amorphous dispersions are an unique and elegant type of system the drug is fully solubilized within the polymer matrix. Quantitative characterization of crystallization in amorphous solid dispersion drug tablets using xray microcomputed tomography volume 24 supplement shawn zhang, joseph neilly, aiden zhu, jacie chen, gerald danzer.
The term solid dispersion refers to a group of solid products consisting of. The conference held in june 2016 was a tribute to the groundbreaking work of emeritus professor and dean george zografi of school of pharmacy, university of wisconsinmadison. The number of papers reporting the preparation of sds has rapidly increased over the last decade, as shown in figure 1b. Furthermore, these actions of solid dispersions can potentially mitigate the achlorhydric effect, one of the root causes of low bioavailability observed from basic compounds 14,15. The term solid dispersions has been defined in the early 1970s by chiou and riegelman as a dispersion of an api in an inert carrier in the solid state prepared by solvent, melting or solvent. The drug can be dispersed molecularly, in amorphous particles clusters or in crystalline particles by. If the drug and polymer are miscible in their fluid. Kyeremateng oliver heinzerling matthias degenhardt gabriele sadowski. Pdf assessing the performance of amorphous solid dispersions. The aim of the current study was to prepare an amorphous solid dispersion of ketoprofen in polymer pvp k30 by solvent coevaporation technique and to characterize the physicochemical properties.
Applications of solid dispersions pharmaceutical research. A novel tablet formulation containing an amorphous solid dispersion asd of elacridar hydrochloride was developed with the purpose to resolve the drugs low solubility in water and to conduct proofofconcept clinical studies. The rapid release of poorly watersoluble drugs from amorphous solid dispersion asd is often associated with the generation of supersaturated solution, which provides a strong driving force for precipitation and results in reduced absorption. Enhancement of oral bioavailability and solid dispersion. Solid dispersion is an effective way of improving the dissolution rate of poorly water soluble drugs and hence its bioavailability. Polymersurfactant system based amorphous solid dispersion. Impact of surfactants on the crystallization of aqueous.
It is important that the resultant spray dried particles do not crystallize during formulation, storage, and upon administration. Yarger research advisor discusses with brandon blass and dr. Both aqueous and nonaqueous dispersions are discussed and the two main procedures used, namely condensation and dispersion methods, are described. In the case of an asd, a crystalline form of the compound is converted to an amorphous form, which is dispersed in, and stabilised by, a carrier. The solid dispersion showing better release profile was chosen to formulate into a tablet dosage form of weight 600 mg. Fundamental aspects of solid dispersion technology for. New directions in pharmaceutical amorphous materials and. Amorphous solid, any noncrystalline solid in which the atoms and molecules are not organized in a definite lattice pattern. However, the matrix can either be crystalline or amorphous. The technology is the science of dispersing one or more active ingredients in an inert matrix in the solid stage. Mechanisms of increased bioavailability through amorphous. Solid solution and dispersion types the drug may be molecularly dissolved in the solid excipient matrix i. Solid state chapter class 12thcrystallization in solids amorphous solids solid state chemistry.
Classification of solid dispersion on the basis of carrier used figure 2. The use of amorphous solid dispersions asd to overcome poor drug solubility has gained interest in the pharmaceutical industry over the past decade. Anomalous transittime dispersion in amorphous solids. Solid dispersion techniques pdf solid dispersion is one of these methods, which was most widely and successfully. By dispersing the drug on a molecular level in a polymeric. The preparation of sds, by which a drug is dispersed in a carrier to make it amorphous, is one of the most. Impact of polymer type and relative humidity on the long. Solid dispersion technique for improving solubility of. Fundamental aspects of solid dispersion technology for poorly. Theory and practice is a valuable reference to pharmaceutical scientists interested in developing bioavailable and therapeutically effective formulations of poorly soluble molecules in order to advance these technologies and develop better medicines for the future.
While including amorphous solid dispersion asd in tablet formulations is increasingly common, tablets containing high asd loading are associated with slow disintegration, which presents a challenge to control pill burden for less potent compounds. 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. The sulfonamides selected were sulfathiazole stz, sulfadimidine sdm. A modified solvent method for preparation of solid dispersions. Asds are challenging to formulate because they are thermodynamically unstable, and the dispersed drugs tend to recrystallize. Pdf on feb 26, 2018, prashant jalindar ghule and others published amorphous solid dispersion. Excipients selection for amorphous solid dispersions youtube. Numerous methods are existing to prepare the solid dispersions such as melting method, solvent evaporation method, fusion method, kneading method.