Polymers make up also many of the materials in living organisms, including, for example. The label and tape industry is one of the most dynamic markets for the application of waterbased polymer dispersion. Solid dispersions are classified by various ways viz. Urea and sugars were the first crystalline carriers that were used in the preparation of solid dispersions. The ethylene polymers used in the practice of this invention are the normally solid polymers of ethylene obtained, for example, by polymerizing ethylene. Dispersions of relatively high solids and good stability were prepared both from typical biodegradable polymers, such as pla, pha and pcl, and from polysaccharides, such as starch and xylan. Single ingredient dry liquids are often used when using a liquid is not desirable.
Some of the major polymers used pharmaceutically to prepare amorphous dispersions include polyvinyl pyrrolidone pvp, hydroxypropyl methylcellulose hpmc, hpmc phthalate, and polyethylene glycolpeg. Impact of polymer type and relative humidity on the long. This invention relates to dispersions of polymeric materials and more particularly to improved dispersions of normally solid polymers from ethylene. Solid solutions and dispersions are used in many routes of drug administration, such as oral, mucosal vaginal, rectal, buccal, ocular, subcutaneous, subdermal, and transdermal, and can help alleviate some of these issues. 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. Amorphous materials can include amorphous drug substance 1, amorphous solid. Amorphous solid dispersions as enabling formulations for. Amorphous solid dispersions amorphous solid dispersions combine the increased solubility of an amorphous material and the improved physical stability of more stable solid forms. Jan 21, 2020 solid solutions and dispersions are generally made by the melt method or the solution method. Mechanisms of increased bioavailability through amorphous. Solid dispersion refers to the dispersion of one or more drug substances in an inert carrier a matrix in the solid state, prepared by melting, solvent evaporation, or meltsolvent methods 1115. 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. Impact of polymer type and relative humidity on the longterm physical stability of amorphous solid dispersions. Amongst the preferred formulations techniques, drugpolymer complexation in the form of solid dispersion is considered most suitable approach for solubilizing bcs class ii compounds yu et al.
Clonazepam was used as a model drug to evaluate its release characteristics from different matrices. First generation solid dispersion these solid dispersions are prepared by using crystalline carriers. Enhancement of solubility and dissolution properties of. Enhancing dissolution profile of diazepam using hydrophilic. The increased porosity of solid dispersion particles also hastens the drug release profile. Fda and medical grade compliant chemical dispersions are available. Methods of preparation solid solutions and dispersions are. Ashlands plasdone povidone polymers are widely used in preparing solid dispersions by melt extrusion and spray drying, as the inhibitory effect of. An overview to modify bioavailability of poorly water soluble drugs ruchi tiwari1. Polymer amorphous salt solid dispersions of ciprofloxacin. The polymer dispersions industry group has many years of experience in supplying antifoams and emulsifiers for the production of emulsion polymers as well as suspension polymers. Introduction solubility is a significant physicochemical factor affecting absorption of drug and its therapeutic effectiveness. Eudragit e100 and hpmc were found to delay both dpd precipitation initiation time and precipitation rates. Aqueous dispersions from biodegradablerenewable polymers.
Production of polymer dispersions additives for polymer. Solid dispersions can be a successful way to enhance the bioavailability of poorly soluble drugs. Through polymer screening, pvp k30 andor soluplus were selected and. Preparation and properties of high solid content and low. Second, to compare the release rate and crystallization tendency of celecoxib amorphous solid dispersions asds formulated with a single polymer, or binary polymer combinations. Common cellulosebased polymers used in spraydried dispersions sdds include hypromellose acetate succinate hpmcas and hydroxypropylmethyl cellulose hpmc. By preparing solid dispersions, it is possible to provide better. These have a disadvantage of being thermodynamically unstable and they do not release drug at a faster rate. Processing impact on performance of solid dispersions. Furthermore, the lack of a unified nomenclature hampers the interpretation and classification of research data. To improve the bioavailability of poorly soluble active pharmaceutical ingredients apis, these materials are often integrated into a polymer matrix that acts as a carrier. Solutions wi th different types of polymers and different drug loads were sprayed. Molecular aspects of drugpolymer miscibility and drugpolymer interactions are also discussed. Here 60 solid dispersion formulations were produced using ten chemically diverse, neutral, poorly soluble drugs, three commonly used polymers, and two manufacturing techniques, spraydrying and melt extrusion.
The solid content of pua copolymers decreases gradually from higher puac ratios to lower ones. Solid state nuclear magnetic resonance studies of hydroxypropylmethylcellulose acetyl succinate polymer, a useful carrier in pharmaceutical solid dispersions. Since the specific type of emulsifier used determines the type of defoamerantifoam required, evonik offers not only a broad range of emulsifiers but also an equally. Engineering of nanofibrous amorphous and crystalline solid. Solid dispersions were prepared by using polyethylene glycol 6000 peg 6000, hpmc, hpc and poloxomer in. Solubility improvement of progesterone from solid dispersions. Amorphous solid dispersions asds can increase the oral bioavailability of poorly soluble drugs. Pure amorphous drugs are rarely used in formulation. Use of polymer combinations in the preparation of solid dispersions of a thermally unstable drug by hotmelt extrusion article pdf available july 20 with 193 reads how we measure reads. Aug 01, 2019 polymers used for the preparation of the solid dispersions are usually amorphous and thermoplastic with specific glass transition temperatures t g. 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. Methods of preparation solid solutions and dispersions are generally made by the melt method. 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. A systematic approach was adapted for the overall formulation development.
Natural polymers hydroxypropylmethylcellulose, ethyl cellulose, starch derivatives like cyclodextrin. Polymer dispersions additives for polymer dispersions. Classification of solid dispersion on the basis of carrier used figure 2. They found that in about 80 % of all cases, amorphous solid dispersions led to improved bioavailability. Pdf use of polymer combinations in the preparation of solid.
Amorphous solid disperions can be used in early animal studies and in marketed products. First, to evaluate the effectiveness of selected polymers in inhibiting solution crystallization of celecoxib. Pdf use of polymer combinations in the preparation of. Solid solutions and dispersions are generally made by the melt method or the solution method. 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 sekiguchi and obi sekiguchi, 1961. Fundamental aspects of solid dispersion technology for poorly. Like cip, xray amorphous solid dispersions were obtained when enro was ball milled with acidic polymers, whereas the use of neutral polymers resulted in semicrystalline products. Impact of polymer type and relative humidity on the longterm.
Hme has been used to prepare solid dispersion of various apis, where polymers or lipids are used as carriers 1. Most of the polymers used in solid dispersions can absorb moisture, which may result in phase separation, crystal growth or conversion from the amorphous to the crystalline state or from a metastable crystalline form to a more stable structure during storage. As a waterinsoluble drug, 40 and 160 mg doses of tel tablets exhibited bioavailabilities of 42% and 58%, respectively. Compared to single polymers, polymer combinations may benefit the manufacture of amorphous solid dispersions by improving drugpolymer miscibility and decreasing the processing temperature. Overcoming excipient challenges in spraydried dispersions. Aqueous polymer dispersions are used for coating of paperboard to provide barrier properties or binding potential. Polymeric amorphous solid dispersions journal of pharmaceutical. Kyeremateng oliver heinzerling matthias degenhardt gabriele sadowski. The objective of the study was to prepare solid dispersions containing a thermally unstable drug by hotmelt extrusion hme. In solid dispersions, drugs are presented as supersaturated solutions after system dissolution, and it is speculated that, if drugs precipitate, it is as a metastable polymorphic form with higher solubility than the most stable crystal form. The initial solid dispersion was prepared via the spraydrying process. Solid dispersions of felodipine, the model drug, were successfully fabricated using fdm 3d printing with polymer blends of peg, peo and tween 80 with either eudragit e po or soluplus. Helps readers understand amorphous solid dispersions and apply techniques to particular pharmaceutical systems covers physical and chemical. As pva is one of most widely used polymers in fdm 3d printing, a pva based.
Polymeramorphous salt solid dispersions of ciprofloxacin. Jan 01, 2011 amorphous solid dispersions asds are particularly attractive for many poorly soluble drug candidates because these formulations offer many of the advantages of more conventional solid oral dosage forms but they also provide faster dissolution rates and higher drug concentrations in the gastrointestinal milieu 3. The development of stable solid dispersion formulations that maintain desired improvement of drug dissolution rate during the entire shelf life requires the analysis of drugpolymer solubility and miscibility. To address this challenge, several strategies based on formulation in polymers have been used to make amorphous solid dispersions asds. Molecular aspects of drug polymer miscibility and drug polymer interactions are also discussed. 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. Multiple linear regression modeling to predict the. Pdf solid dispersions as a drug delivery system researchgate. This indicates no possible interaction between the polymers and terbinafine hydrochloride. The purpose of this study was to investigate the synergistic effect of polymers and drugpolymers interactions on the improved stability and bioavailability of telmisartan tel ternary solid dispersions.
These raw materials are used in formulations for adhesives, architectural coatings, automotive coatings, building materials, construction coatings, industrial coatings, nonwovens, printing and packaging, paper coatings. Classification of solid dispersion on the basis of miscibility of drug and polymers. Dispersions would allow alternative application techniques for biopolymers, thin coatings and freedom for the formulation. Methods and polymers to increase the solubility of. Sds were prepared using solventevaporation technique and characterized by powder xray diffraction pxrd and mdsc. Solid dispersion is molecular dispersion of drug in a polymer matrix which leads to improved solubility and hence better bioavailability. Additionally, the paper collates information on types of polymers used for the generation of amorphous solid dispersions, their structural attributes and mechanisms of stabilization of amorphous form of drug by polymers. The aim of this contribution was to evaluate the impact of processing methods and polymeric carriers on the physicochemical properties of solid dispersions of the poorly soluble drug progesterone pg. The thermograms of solid dispersions display the characteristic features of the drug. Applications of solid dispersions pharmaceutical research. Taking account of its currently mostused form table 1, a solid dispersion can now be more narrowly defined as dispersion of drug in an amorphous polymer. Solidstate miscibility studies were carried out using modulated differential scanning calorimetry mdsc.
Drugexcipient behavior in polymeric amorphous solid dispersions. Polymers make up also many of the materials in living organisms, including, for example, proteins, cellulose, and nucleic acids. An investigation into the use of polymer blends to improve. The selection of polymer and processing temperature are important concerns in the preparation of solid dispersions containing a thermally unstable drug by hme. Carbamazepine cbz was selected as model drug and combinations of kollidon va64 va64, soluplus sol and eudragit epo epo were utilized as carriers. Dec 27, 2019 to address this challenge, several strategies based on formulation in polymers have been used to make amorphous solid dispersions asds. Dispersions today are based on synthetic polymers poorly degraded in a biological environment. The sulindacpolymerplasticizer combination that was.
Solid dispersions are similar to a group of solid products consisting of at least two different components. These have a disadvantage of being thermodynamically. Stability and bioavailability enhancement of telmisartan. In first generation solid dispersions crystalline carriers such as urea and sugar, used in the solid dispersion preparation. There are several types of solid dispersion that have been used for pharmaceutical purposes, as summarized in table 1. The ethylene polymers used in the practice of this invention are the normally solid polymers of ethylene obtained, for example, by polymerizing. Based on our special knowhow about interfacial chemistry we offer high performance additives for polymer adhesives controlling processes like. In this work, the phase behaviors of solid dispersions were investigated as a function of the api as well as of the type and molecular weight of the carrier polymer. Infrared, raman spectroscopy and molecular modeling were used to investigate drugpolymer interactions in the dispersions. Correlating the behavior of polymers in solution as. Apr 11, 20 solid dispersions were characterized by x. To improve the pharmaceutical properties of amorphous ciprofloxacin cip succinate salts via formulation as polymer amorphous salt solid dispersions assds. The results show that pcsaft predictions are in a good accordance with the experimental data, and pcsaft can be used to predict the whole phase diagram of an apipolymer solid dispersion as a function of the kind of api and polymer and of the polymers molecular weight.
Drugpolymer miscibility, interactions, and precipitation. These raw materials are used in formulations for adhesives, architectural coatings, automotive coatings, building materials, construction coatings, industrial coatings, nonwovens, printing and packaging, paper coatings, and wood coatings. The solid dispersions were prepared by solvent method. Polymers used for the preparation of the solid dispersions are usually amorphous and thermoplastic with specific glass transition temperatures t g. Polymer dispersions additives for polymer dispersions from. In 10 % of the cases no improvement was found and in approx.
Polymerics can apply the main ingredient liquid to a silica carrier to produce a powder form that is typically 5070% active main ingredient. Thermodynamic phase behavior of apipolymer solid dispersions. Formulation and characterization of solid dispersion. However, the matrix can either be crystalline or amorphous. 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. Use of polymer combinations in the preparation of solid. Multiple methods for preparing solid dispersions have been reported. Analytical and computational methods for the estimation of. If the selected drug is crystalline, it usually preserves this state in physical mixtures with the polymer, which is evident on the dsc thermogram of the physical mixture as sharp endothermic peak. Distilled water was used as dissolution media, ml of distilled water was used as dissolution medium in each dissolution basket at a temperature of 37c and a paddle speed of 100 rpm. The resulting mixture is called a solid dispersion.
The effectiveness of polymers, polyvinylpyrrolidone pvp. Currently, the methods of most interest are melt extrusion and spray drying. Basfs dispersions and resins business offers a wide range of highquality binders, resins, additives and colorants worldwide. These solid dispersions are thermodynamically more stable and did not release the drug as quickly as amorphous ones. Dec 30, 2019 amorphous solid dispersions asds can increase the oral bioavailability of poorly soluble drugs. Formulation development would lead to be failure if drug having poor aqueous solubility. Drugs and polymers in dissolving solid dispersions. Based on our special knowhow about interfacial chemistry we offer high performance additives for polymer adhesives controlling processes like defoaming, deaerating and wetting. Widely used pyrrolidone polymers include polyvinylpyrrolidone pvp, also known as polyvidone or povidone and copolymers of pvp with vinyl acetate. Use of polymer combinations in the preparation of solid dispersions. Drugexcipient behavior in polymeric amorphous solid. The excipients in these formulations are usually polymers, but small molecules such as urea. Thus, ssnmr relaxometry will provide a better understanding of drugpolymer intimacy in the solid dispersion which helps in improving the stability of amorphous solid dispersions and preventing phase separation over the shelf life of the product. Dispersions had specific properties making them interesting in future as possible total or partial replacement of synthetic dispersions in coatings.
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