As a result, numerous techniques numerous chemical and physical modificationshave been developed to enhance the solubility of these poorly soluble drugs. Pdf solid dispersions have been employed to enhance the dissolution rates of poorly watersoluble drugs. Development, characterization and solubility enhancement of comparative dissolution study of second generation of solid dispersions and microspheres for poorly water soluble drug. Low aqueous solubility always results in a slow drug dissolution rate in the. Development, characterization and solubility enhancement. Enhancement of solubility of poorly water soluble drug by. Swami vivekananda college of pharmacy, near toll naka, khandwa road indore m.
Currently only 8% of the new molecules have both high solubility and permeability. Formulation and processing technologies for dissolution. Dissolution enhancement of poorly water soluble drugs by. Enhancing permeability of poorly permeable drugs 1. Therefore, enhancing solubility and ba of poorly watersoluble drugs in bcs classes ii and iv is a significant challenge in the pharmaceutical. In case of poorly water soluble drug, dissolution may be the rate limiting step in the process of absorption. Various techniques are used for the enhancement of the solubility of poorly soluble drugs which include physical and chemical modifications of drug and other methods like particle size reduction. The solubility is defined as a maximum quantity of solute that can dissolve in a certain quantity of solvent or quantity of solution at a specified temperature 2. Aqueous solubility is a limiting factor in the oral bioavailability of a certain class of poorly water soluble drugs. Ebscohost serves thousands of libraries with premium essays, articles and other content including solubility enhancement of poorly water soluble drugs. The drugs therapeutic efficacy depends upon the bioavailability and ultimately upon the solubility. Allopurinol is poorly water soluble drug used in treatment of gout. The formulation of poorly watersoluble drugs has always been a. Highly supersaturated aqueous drug solutions are often generated during drug testing and upon delivery to the patient.
Techniques for solubility enhancement of poorly soluble. For the drugs with low aqueous solubility and high permeability the dissolution rate will be the rate limiting step for absorption. Pdf solubility enhancement techniques for poorly water. The drugs which are practically insoluble in water hence show poor bioavailability. Simvastatin by microwave generated solid dispersion. Hence various techniques are used for the improvement of the solubility of poorly water soluble.
Pdf techniques for solubility enhancement of poorly soluble. The formulation of poorly water soluble drugs has always been a challenging problem faced by pharmaceutical scientists and it is expected to increase because approximately 40% or more of the new chemical entities being generated through drug discovery programs are poorly water soluble. The most successful techniques that are employed for. One of the main interests associated with cyclodextrins refers to the enhancement of. The drugs belong to bcs class ii and class iv has problem of solubility, to overcome the solubility problem nanotechnology is most useful technique. The purpose of this research was to improve the solubility of asiatic acid, a poorly water soluble drug, by complexation with hydroxypropyl. Enhancing dissolution of poorly soluble drugs through jet. Besides enhanced solubility and dissolution rates leading to improved bioavailability, other advantages of drug nanoparticles include the. About 40% of drugs developed in the past and about 90% of the drugs in development are poorly soluble drugs. However, it is reported that the swelling ability of the carrier profound influence on the improvement of dissolution rate of poorly watersoluble drugs.
Low aqueous solubility is the major problem encountered with formulation. The formulation of poorly watersoluble drugs has always been a challenging problem faced by. Microwave induced solubility enhancement of poorly water soluble. Basically, drug dissolution is a ratelimiting factor for the oral absorption of poorly watersoluble drugs from git. From amorphous structure replacing crystalline structure 10, 11, 12. Enhancement of solubility and dissolution rate of poorly water. The solubility or dissolution rate of a drug in this category is therefore a key factor in determining the rate and extent of its absorption. Dissolution enhancement, drugpolymer miscibility, solid dispersions.
Solubility enhancement of a poorly aqueous soluble drug ketoprofen using solid dispersion technique nagar gauri, luhadiya aditi, agrawal shikha a, dubey p. As of result, more than 40% newly discovered drug candidates are poorly water soluble and solubility remains a prominent challenge for formulation scientist. Solubility enhancement of poorly water soluble drug simvastatin by. Department of pharmaceutics, rajiv academy for pharmacy, mathura u. If the compound is a brickdust molecule, it typically has a low solubility in lipids, but may have considerable higher solubility in surfactants and co. Oral drug administration is desirable due to good patient convenience and consequently better compliance. The objective of this investigation was to improve solubility and dissolution rate of water insoluble drugs.
Techniques to improve the solubility of poorly soluble drugs. Cd feed ratio by molar on the aqueous solubility was investigated, the. The enhancement of oral bioavailability of poorly water soluble drugs remains one of the most challenging aspects of drug development. A growing number of new therapeutic molecules are limited by low or erratic bioavailability due to poor water solubility. Introduction oral route is most desirable route of administering. Bioavailability enhancement of poorly watersoluble drugs via.
Praveen kumar, and chhater singha study on, solubility enhancement methods for poorly water soluble drugs. Solubility enhancement of a poorly aqueous soluble drug. Pdf techniques for solubility enhancement of poorly. Various techniques are used for the enhancement of the solubility of poorly. A study on solubility enhancement methods for poorly water soluble drugs. Dissolution enhancement of ramipril using water soluble. Solubility enhancement methods a promising technology. The oral dosage forms have many advantages over other types of dosage forms like greater stability, accurate dosage, smaller bulk and easy production is possible. Pdf solubility enhancement of poorly soluble drugs by. Cd were useful to increase solubility and dissolution rate, resulting in enhancement of bioavailability and minimization of gastrointestinal toxicity of drug upon oral administration of inclusion complex. Enhancing solubility and dissolution rate of poorly water soluble drugs 2. Pdf solubility enhancement of poorly soluble drugs by solid.
Enhancement of the solubility of poorly water soluble. To improved local solubility and wettability of the poorly soluble drug in the solid dispersion matrix, 14. The use of hydrophilic polymers as carriers for the dissolution enhancement of poorly water soluble drugs is of increasing interest 1415. Dissolution enhancement of poorly water soluble drugs by coprecipitation in the presence of additives and stabilizers mai khanfar1 and mutaz sheikh salem2 1 department of pharmaceutical sciences, faculty of pharmacy, philadelphia university, amman, jordan. The methods discussed above are able to address the problem of poor aqueous solubility and permeability of drug substances. Jul 05, 2012 dissolution of drug is the rate determining step for oral absorption of the poorly water soluble drugs and solubility is the basic requirement for the absorption of the drug from git. Bioavailability, salt formation, cosolvency, solubilizing agent, micronization, solid dispersion. The solubility behavior of drugs remains one of the most challenging aspects in formulation development. The use of hydrophilic polymers as carriers for the dissolution enhancement of poorly watersoluble drugs is of increasing interest 1415. The complexation of poor water soluble drugs with cyclodextrins has been extensively studied in recent years. To be absorbed from the gastrointestinal gi tract, a drug needs to be dissolved in the gi fluids.
Almost more than 90% drugs are orally administered. Last three decades of drug discovery are governed by combinatorial chemistry and high throughput screening. Solid dispersion is successfully applied to improve the solubility and consequently the bioavailability of poorly water soluble drugs. The samples were exposed to microwave radiation for predetermined durations 3, 4, 5 and 6 minutes. Poorly water soluble drugs often require high doses in order to reach therapeutic plasma concentrations after oral administration kumar sk et. A consequence of low aqueous solubility is a slow dissolution rate.
A study on solubility enhancement methods for poorly water. Drug nanocrystals consists pure poorly water soluble drugs without any matrix. Pharm, royal college of pharmacy and health sciences, berhampur 2asst. The phase behavior of such solutions appears complex and poorly understood, with the formation of colloidal drug aggregates often being reported. Mercuri, enhancing dissolution of poorly soluble drugs through jetmilling, pharmaceutical technology 39 2 2015. Enhancing solubility and dissolution rate of poorly watersoluble drugs 2.
Development, characterization and solubility enhancement of. Professor, royal college of pharmacy and health sciences, berhampur pranab. To enhance the solubility of poorly water soluble drug,by means of solubilising agent. Currently only 8% of new drug candidates have both high solubility and permeability. Poor dissolution rate is the major challenge for formulation and development of solid oral dosage form of poorly water soluble drugs. Jan 03, 2012 enhancement solubility poorly water soluble drug. Dissolution enhancement of poorly water soluble drugs by sateesh kumar sathigari a dissertation submitted to the graduate faculty of auburn university in partial fulfillment of the requirements for the degree of doctor of philosophy auburn, alabama may 9, 2011 keywords. Lipidbased formulations for oral administration of poorly watersoluble drugs. Such drugs can be solubilized by various techniques, which is useful for the enhancement of solubility of poorly water soluble drug and hence, its bioavailability. Poonam kesarwani, sameer rastogi, vijay bhalla, vandana arora. Then the beakers containing the samples were maintained at. Solubility enhancement of a poorly water soluble drug by. Pharmaceutical dispersion techniques for dissolution and. They are highly watersoluble or hydrophilic in nature in the case of poorly watersoluble drugs.
Increasing the dissolution rate could lead to an enhancement in bioavailability and therapeutic effect 11. Technologies to improve the solubility, dissolution and. It is a phenomenon to increase the solubility of poorly water soluble drugs in the blends of hydrotropic agents, which may give miraculous synergistic enhancement effect on solubility of poorly water soluble drugs, utilization of it in the formulation of dosages form of water insoluble drugs and to reduce concentration of. Enhancement of solubility of poorly soluble drug using. Enhancement of the aqueous solubility and permeability of. Enhancement of solubility and dissolution rate of poorly. As a result, much research has been conducted into methods of improving drug solubility and dissolution rates to increase the oral bioavailability of hydrophobic drugs.
Enhancement of solubility and dissolution rate of poorly water soluble drug using cosolvency 351 nonpolar solutes. The solubilizing ability of two aromatic hydrotropes, n,ndiethylnicotinamide dena and n,ndimethylbenzamide dmba, was investigated using a set of poorly soluble, structurally diverse drugs. Because of solubility problem of many drugs the bioavailability of them gets affected and hence solubility enhancement becomes necessary. Formulation and processing technologies for dissolution enhancement of poorly watersoluble drugs. In order to investigate the effect of second generation polymers on the dissolution release mechanism of poorly soluble drugs from solid dispersions sd and microspheres ms, hydrochlorothiazide 6chloro1,1dioxo3,4dihydro2h1,2,4benzothiadiazine7 sulfonamide hct, a poorly water soluble drug 0. The poor solubility and low dissolution rate of poorly water soluble drugs in the. Most of the promising newer chemical entities are poorly water soluble which may present a lack of therapeutic effect, because of their low bioavailability. As a result, nonpolar drugs such as cb can be solubilized most efficiently by peg 400 and ethanol. Because of solubility problem of many drugs the bioavailability of them gets affected and. Methods microwave energy was used to prepare an enhanced release dosage form of the poorly water soluble drug atr with peg 6000 as a. Lipidbased formulations for oral administration of poorly.
Overview of the manufacturing methods of solid dispersion. Enhancement of solubility and dissolution rate of poorly water soluble raloxifene using microwave induced fusion method 573 one beaker was placed at a time inside the microwave oven. The number of aromatic rings in the solute molecule has a very strong effect on the solubility enhancement produced by either hydrotrope. Rapid onset of action of allopurinol drug in treatment of gout is required. Guar gum is used in soliddosage forms as a binder and disintegrant. The various techniques described above alone or in combination can be used to enhance the solubility of the drugs. Hydrotropic solubilization of poorly watersoluble drugs. Poutonformulation of poorly watersoluble drugs for oral administration. Mca of physical mixtures of a poorly watersoluble drug and a suitable pharmaceutical polymer has been described in the past, using mainly highenergy mechanical. Drug with poor water solubility cause slow dissolution rates, generally show erratic and incomplete absorption leading to low bioavailability when administered orally. Many drugs are abandoned due to poor aqueous solubility, although having a potential therapeutic effect. The most successful techniques that are employed for dissolution.
Solubility enhancement methods a promising technology for. Dissolution of drug is the rate determining step for oral absorption of the poorly water soluble drugs and solubility is the basic requirement for the absorption of the drug from git. The objective of the present work was to enhance the solubility and dissolution rate of the drug raloxifene. Griseofulvin tablets, fenofibrate capsules, progesterone capsules, colestipol tablets, glyburide tablets, and estradiol tablets nanosuspensions micronsized particles do not sufficiently enhance the solubility of many poorly soluble drugs. Enhancement of solubility of poorly soluble drugs by using.
For enhancement of solubility and dissolution rate of poorly soluble drugs, abundant commercially viable methods are. The following are some of the marketed products containing micronized drugs. In physical property, lowmolecularweight carriers are generally crystalline e. Dissolution enhancement of poorly water soluble drugs. Pdf solubility enhancement of poorly water soluble drugs by solid. Solubility enhancement technique for poorly water soluble drugs p s argade introduction 1, 2 the simplest and easiest way of administering drug is through oral route. Various techniques are used for the improvement of the aqueous solubility, dissolution rate, and bioavailability of poorly water soluble drugs include micronization, chemical modification, ph adjustment, solid dispersion, complexation, co. These drugs are poorly water soluble however they rapidly pass biological membranes once dissolved. Mechanochemical activation is a practical cogrinding operation used to obtain a solid dispersion of a poorly water soluble drug through changes in the solid state molecular aggregation of drugcarrier mixtures and the formation of noncovalent interactions hydrogen bonds between two crystalline solids such as a soluble carrier, lactose, and a. Solid dispersion formulations of pioglitazone hcl using. The promising results of solid dispersion in solubility and dissolution rate enhancement of poorly soluble drugs can be attributed to various aspects. Pdf the solubility behavior of drugs remains one of the most exigent aspects in formulation development.
Since the absorption of these drugs is dissolution ratelimited their bioavailability can only be. One of these techniques includes the manufacture of amorphous solid dispersions of drug substances in a polymeric carrier. Because of the clinical demand for new and more efficacious anticancer, antiviral, and antiinfective drugs, many of these new drugs must be formulated for injection. I declare that the thesis entitled, solubility enhancement and dissolution method development of some poorly soluble drugs, submitted by me for the degree of doctor of philosophy is the record of research work carried out by me during the period from july 2011 to january 2017 under the supervision of dr. In this study, the phase behavior of eight hydrophobic poorly watersoluble drug molecules in highly supersaturated aqueous. However, it is reported that the swelling ability of the carrier profound influence on the improvement of dissolution rate of poorly water soluble drugs. From these findings, inclusion complexes of poorly watersoluble npx with 2hp. Basically, drug dissolution is a ratelimiting factor for the oral absorption of poorly water soluble drugs from git. Enhancing dissolution of poorly soluble drugs through jetmilling. To enhance solubility of poorly water soluble drugs journal of applied pharmaceutical research january march 2017 volume 5 issue 1 3 valid for powders of daily life with a size in the micrometer. Solid dispersion is a unique and promising approach for enhancing the dissolution characteristics and oral bioavailability of poorly water soluble drugs. When referring to this article, please cite it as p. Liquidliquid phase separation in highly supersaturated.
Key words bioavailability, novel methods, solubility, solubility enhancement. Injectable formulations of poorly watersoluble drugs. Methods and polymers to increase the solubility of. Limbachiyatechniques solubility enhancement poorly soluble drugs. When administered orally, a drug has to first dissolve in gastrointestinal fluids before it can be absorbed in to the blood and reach its site of action. The bioavailability of many poorly watersoluble drugs is limited by their dissolution rates which are in turn controlled by the effective surface area present for dissolution. Hence various techniques are used for the improvement of the solubility of poorly water soluble drugs include hydrotrophy, use of salt form, use of precipitation inhibitors, alteration of ph of the drug microenvironment, solvent deposition, precipitation ph adjustment. Solubility enhancement techniques solubility of poorly soluble drugs can be improved by using various techniques. Therefore, solubility enhancement of poorly water soluble drugs is one of the necessary preformulation steps in the pharmaceutical product development research. School of pharmacy, lloyd institute of management and technology, plot no11, knowledge park2, greater noida206, uttar pradesh, india. Mechanochemical activation is a practical cogrinding operation used to obtain a solid dispersion of a poorly water soluble drug through changes in the solid state molecular aggregation of drugcarrier mixtures and the formation of noncovalent interactions hydrogen bonds between two crystalline solids such as a soluble carrier, lactose, and a poorly soluble drug, indomethacin, in order to. Techniques for solubility enhancement of poorly soluble drugs. Numerous methods have been followed to improve the dissolution rate of poorly water soluble drugs. Abstract it is generally recognized that poor solubility is one of the most frequently encountered difficulties in the field of pharmaceutics.
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