Submitted to the graduate faculty as partial fulfillment of the requirements for the. Furosemide exhibited a characteristic, sharp exothermic peak at 224. 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. It is very slightly soluble in water and hence orally administered drug is less bioavailable. Sekiguchi and obi were the first to describe on solid dispersions in 1961. Cellulosebased amorphous solid dispersions enhance.
Solubility improvement by solid dispersion and their. Solid dispersions have attracted considerable interest as an efficient means of improving the dissolution rate and hence the bioavailability of a range of poorly watersoluble drugs. Formulation, physicochemical evaluation, and dissolution. Factors affecting the formation of eutectic solid dispersions and their dissolution behavior. The relationship between amorphous solubility and supersaturation was examined and correlated to the dissolution of amorphous solid dispersions. 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. Professor tamara minko improving oral bioavailability of poorly watersoluble drugs remains one of the most challenging aspects of drug development.
The suitability of a number of polymers and small molecules as stabilizers for cip was examined. Solubility screenings of various polymers and acidifiers were performed to select appropriate excipients for the sd. Seibold the ohio state university 2005 honors thesis committee. The objective of this study was to prepare aripiprazole ariloaded solid dispersions sds to enhance solubility and dissolution via hotmelt extrusion hme technology. Formulation, characterisation, permeability and genomic evaluation muhammad sheraz akbar khan doctor of philosophy aston university march 2010 this copy of the thesis has been supplied on condition that anyone who consults it is understood to recognise that its.
Cellulosebased amorphous solid dispersions enhance rifapentine delivery characteristics and dissolution kinetics in vitro christopher j. Then, 50 ml of methanol were measured using a measuring cylinder and transferred into a 400 ml beaker. Ari was chosen due to its poorly watersoluble properties. The drug was solubilized by surfactants andor polymers then adsorbed onto the. Physicochemical characterization of solid dispersions of indomethacin with peg 6000, myrj 52, lactose, sorbitol, dextrin, and eudragit e100, drug development and industrial pharmacy. The characterization of cannabidiol amorphous solid. Factors affecting the stability and performance of. In recent years the pharmaceutical industry has seen a rise in the number of drug compounds with low aqueous solubility, and consequently poor oral bioavailablility. I declare that the thesis entitled, solubility enhancement and dissolution method. 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 method, solvent, or melting solvent method. 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.
Fully xray amorphous solid dispersions were only obtained when cip was ball milled with acidic polymers such as eudragit l100, eudragit l10055, carbopol and hpmcas. Razia begum department of pharmaceutical technology, shri vishnu college of pharmacy, vishnupur, bhimavaram534202, ap, india. Theses and dissertationspharmacy, university of kentucky. More recently, nonaqueous dispersions of magnetic oxides have attracted considerable attention as a result of their applications in the. Amorphous solid dispersion effects on in vitro solution. In this thesis, the hypothesis that a number of drugdrug and drug. University, in particular my thesis advisors bozena michniakkohn and fernando. It indicates that the drug is uniformly dispersed in the powder formulation.
Solid dispersion by this method is composed of active ingredient and carrier, and prepare by hotstage extrusion using a corotating twinscrew extruder. Improved solubility and dissolution of bcs class ii drug spironolactone by formulating in ternary solid dispersion with carrier. Thesis for submission correction approved date correct. Characterization of ternary solid dispersions of itraconazole.
The physicochemical methods used here suggested that improvements in. Preparation and characterization of cefuroxime axetil. Pdf solubility is a significant physicochemical parameter that affects the absorption. Dissolution behavior of amorphous solid dispersions by. The first description of solid dispersions was from sekiguchi and obi in 1961. Physicochemical characterization and dissolution studies. Solid dispersion a novel approach for enhancement of. Solubility improvement by solid dispersion and their characterization. One potential solution to this problem is to formulate such compounds as solid dispersions, whereby the drug is dispersed in a carrier matrix in the solid state. Analysis of pharmaceuticalpolymer solid dispersions produced by supercritical carbon dioxideassisted techniques a thesis presented in partial fulfillment of the requirements for graduation with distinction at the ohio state university by maren l.
Solid dispersions project thesis proposal i help to study. Solid dispersion formulations with different carriers including crospovidone, microcrystalline. Physicochemical characterization of binary and ternary solid. 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 solid dispersions are one of the most successful strategies to improve drug release of poorly soluble drugs. The following work provides evidence for generating homogenous glass phase amorphous solid dispersions containing 50% ww up to 75% ww cbd concentrations in the domain size of 2 5 nm.
Solid dispersions in watersoluble carriers have attracted considerable interest as a means of improving the dissolution rate, and hence possibly bioavailability, of a range of hydrophobic drugs. The inclusion of supercritical fluids, such as carbon dioxide, in the polymermelt extrusion method has proved to significantly lower processing temperatures, thereby extending the technique to thermolabile compounds. The research says inclusion of drug inside the polymeric matrix, ratio of drug to polymer and physicochemical qualities from the drug molecules boost the dissolution rate. Solid dispersion technique for improving solubility of some poorly soluble drugs mogal s.
Enhancement of dissolution rate of glimepiride using solid. In the same decade, several solid dispersions were described using poorly water soluble drugs, such as sulfathiazole and chloramphenicol using urea as high water. Concentrations up to 85% ww cbd were concluded homogenous in the supercooled liquid phase in domain sizes of 20 30 nm. To enhance the solubility of ler two methods namely solid dispersion and. Dropping method solution the dropping method, developed by ulrich et al. Solid dispersions were prepared using polyvinyl pyrrolidone pvp, polyethylene glycol1500 peg1500 and polyethylene glycol4000peg4000 to increase its aqueous solubility. The poor solubility of carvedilol leads to poor dissolution and hence variation in bioavailability. An overview to modify bioavailability of poorly water soluble drugs ruchi tiwari1, gaurav tiwari1, birendra srivastava2 and awani k. Solid dispersions of poorly watersoluble drugs with watersoluble carriers have been reduced the incidence of these problems and enhanced dissolution. In order to enhance the bioavailability it is necessary. The work presented within this thesis is focused on developing the techniques necessary for studying complex phase behavior through the investigation of a model drug system. The effects of solid dispersions sd on the solubility of rutin were studied. The water soluble carriers used in preparation of solid dispersion enhance the. Formulation, physicochemical evaluation, and dissolution studies of carbamazepine solid dispersions m.
Enhancement of dissolution rate of glimepiride using solid dispersions with polyvinylpyrrolidone k 90 s. Jeff yarger, chair greg holland gary moore arizona state university may 2019. The methods presented in this thesis provide a new avenue towards better understanding of the behaviour of solid dispersions, which in turn may result in more. This beaker was left on a hotplate stirrer which had been turn off its temperature while set to stir at. Enhancement of limepiride dissolution profile by solid dispersion. After slow cooling, the ampoules caps were opened and the solid dispersions collected. Solid dispersion is one of the important strategies to tackle dissolutionratelimited oral absorption of poorly soluble compounds. However, products made by solution polymerization also lend themselves to the production of waterborne secondary acrylic dispersions and powder coatings. A formulation strategy to enhance dissolution rate of poorly watersoluble ionic drugs by anasuya a. Peg 8000 was selected like a carrier within the solid dispersions. The characterization of cannabidiol amorphous solid dispersions by brandon blass a thesis presented in partial fulfillment of the requirements for the degree master of science approved march 2019 by the graduate supervisory committee. The production and characterization of fluoroquinolone. Improved solubility and dissolution of bcs class ii drug. All the physical mixtures and solid dispersions showed the presence of high drug content and low standard deviations of the results.
This is to certify that the dissertation entitled enhancement of. All dispersions were pulverized with a pestle and mortar, passed through sieve no. Formulation and evaluation of solid dispersions of. 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. Studies of the solubility of rutin from solid dispersions. Physicochemical characterization of solid dispersions. Cyclodextrin and adjuvant water soluble vitamin pyridoxine hcl vit b6 by. The present study is aimed at improving the dissolution of poorly watersoluble drug, aceclofenac. Analysis of pharmaceuticalpolymer solid dispersions. Abstract the main aim of this thesis was to investigate the feasibility of hme to manufacture solid dispersions of poorly soluble drugs, bicalutamide bl and celecoxib cx, and to characterize the physicochemical properties of the prepared melt extrudates by different analytical techniques. Formulation of solid dispersions of cefuroxime axetil. Amorphous solid dispersion effects on in vitro solution concentrations of quercetin by andrew d. By preparing solid dispersions, it is possible to provide better.
Application of dropping method in formulation of solid dispersions. Solidliquid dispersions, also known as suspensions, are widely used in industry. Gilley thesis submitted to the faculty of virginia polytechnic institute and state university in partial fulfillment of the requirements for the degree of masters of life science in food science and technology approved by. Murthy royal college of pharmacy and health sciences, andhapasara road, berhampur 760002, orissa, india corresponding author. Flexible continuous manufacturing platforms for solid dispersion formulations. There are several types of solid dispersion that have been used for pharmaceutical purposes, as summarized in table 1. Chapter6 preparation and characterization of solid. Drugs and polymers in dissolving solid dispersions. Applications of solid dispersions bindu yadav 1 and y. The proposed matrix material, pluronic, is a block copolymer is used for diverse pharmaceutical applications. Preparation of a solid dispersion by a dropping method to improve the rate of dissolution of.
Both aqueous and nonaqueous suspensions are used in paints, dyestuffs, inks, cosmetics, detergents, and pharmaceuticals. Rai1 1pranveer singh institute of technology, dept. Solid dispersion technique for improving solubility of. The concentration of drug in the dispersions is always 40% ww. Solid dispersions were prepared using various drugs to polymer ratios. Solid dispersions of telmisartan were prepared by surface solid dispersion method using polymers like poloxamer 407, peg 6000 by solvent evaporation method. Besides, the antioxidant activity of the quercetinpvp k25 solid dispersions dissolved in aqueous solution and pure quercetin dissolved in methanol showed ic50 value of 0.
The term solid dispersion refers to a group of solid products consisting of. The solubility of rutin from sd increased by a factor of 52. Development and characterization of solid dispersion of piroxicam. 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 solventmelting methods. Design and performance of felodipinebased solid dispersions. This thesis focuses on factors affecting the stability and performance of amorphous solid dispersions asds of poorly soluble active pharmaceutical ingredients apis. They noted that the formulation of eutectic mixtures improve the rate of drug release and, consequently, the bioavailability of poorly water soluble drugs. Winslow abstract academic the efficacy of rifapentine, an oral antibiotic used in the treatment of tuberculosis, is reduced due to its degradation at. Drug content of the solid dispersions was found to be between 94. One can of course argue about the use of the term solid state if amorphous systems are considered. Peg 8000 was selected as a carrier in the solid dispersions. Preparation and evaluation of aripiprazoleloaded ph. Preparation and characterization of solid dispersions of. Rutin and its sd with polyethylene glycol 1500 and polyvinylpyrrolidone 0 were studied.
Solid dispersion is molecular dispersion of drug in a polymer matrix which leads to improved solubility and hence better bioavailability. The sulindacpolymerplasticizer combination that was. 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. Preparation of sd increased the solubility and rate of dissolution of the active substance. Solidstate characterization of nifedipine solid dispersions. Formulation and characterization of solid dispersion. This technique may overcome some of the difficulties. The study revealed that inclusion of drug within the polymeric matrix, ratio of drug to polymer and physicochemical properties of the drug molecules enhance the dissolution rate.
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