data published in the literature or available to us from discussions range from fold what are the factors affecting the increase in saturation solubility? the factors can be identified when looking at the theoretical background the kelvin equation describes the increase in the vapor pressure of droplets in a gas allegra online medium as a function of their particle size, ie as a function of their curvature fig the kelvin equation p = vapor pressure po = equilibrium pressure of a flat liquid surface � = surface tension vl = molar volume cos = contact angle rk = radius of droplet r = universal gas constant t = absolute temperature k the vapor pressure increases with increasing curvature of the surface, that means decreasing particle size each liquid has its compound specific vapor pressure, thus the increase in vapor pressure will be influenced by the available compound specific vapor pressure the situation of a transfer allegra online of molecules from a liquid phase droplet to a qas phase is in principal identical to the transfer of molecules from a solid phase nanocrystal to a liquid phase dispersion medium the vapor pressure is equivalent to the dissolution pressure in the state of saturation solubility, there is an equilibrium of molecules allegra online dissolving and molecules recrystallizing this equilibrium can be shifted in case the dissolution pressure increases, thus increasing the saturation solubility identical to liquids with different vapor pressures under normal conditions micrometer droplet size, each drug crystal has a specific dissolution pressure in micrometer size relative vapor pressure at � nlpin ��� allegra online � t droplet size [��] fig comparison of the relative increase in vapor pressure between water, ether and oleic acid calculated using the kelvin equation as a function of the droplet size with permission after the important question is how the dissolution pressure changes, depending on the specific dissolution pressure of each allegra online compound and on the particle size model calculations were performed applying the kelvin equation to compounds with different vapor pressures droplets as a function of droplet size fig liquids with low medium and high vapor pressure were selected, such as oleic acid as an oil, water and ether the important result allegra online for a drug formulation was the increase in vapor pressure is more pronounced for compounds having a priori a low vapor pressure applied to solid compounds, increase in dissolution pressure will be more pronounced for compounds having a priori a low dissolution pressure, ie the relative increase is highest for poorly soluble allegra online drugs the increase in vapor pressure is exponential, with a very pronounced increase occurring at droplet sizes below nm figure shows a calculated increase for barium sulfate as solid model compound does size really matter transferring this to drug nanocrystals means that really smart crystals with highest increase in saturation solubility allegra online should have a size of eg nm or nm from this, it can be concluded that the slogan size matters is correct regarding the increase in saturation solubility, and consequently, the increase in dissolution saturation solubility of bas in water at � drug size [jam] fig increase in saturation solubility of bas allegra online in water as a function of the particle size calculated using the kelvin equation with permission after velocity caused by a higher cs it needs to be kept in mind which blood profile is anticipated with a certain drug in many cases, too fast a dissolution is not desired creation of allegra online high plasma peaks, reduction of tmax there is the request to combine drug nanocrystals with traditional controlled release technology eg coated pellets to avoid too fast a dissolution, too high plasma peaks, too early a tmax and to reach prolonged blood levels to summarize, the optimal drug nanocrystal size will depend on allegra online required blood profile administration route in the case of iv injected nanocrystals, the size should be as small as possible in case the pharmacokinetics of a solution should be mimicked in the event that a targeting is the aim eg to the brain by pathfinder technology, the drug nanocrystals should possess allegra online a certain size to delay dissolution and to give them the chance to reach the bloodbrain barrier bbb for internalization by the endothelial cells of the bbb effect of amorphous particle state it is well known that amorphous drugs possess a higher saturation solubility, compared with crystalline drug material a classical example allegra online from the literature is chloramphenicol palmitate the polymorphic modification i has a solubility of , the high energy modification ii a solubility of and the amorphous material of mgml the same is valid for drug nanoparticles, amorphous drug nanoparticles possess a higher saturation solubility, compared with equally sized drug nanocrystals in the allegra online crystalline state therefore, to reach highest saturation solubility increase, a combination of nanometer size and amorphous state is ideal however, prerequisite for exploitation in pharmaceutical products is that the amorphous state can be maintained for the shelf life of the product production methods precipitation methods hydrosols the hydrosol technology was developed by sucker and the intellectual property owned by the company sandoz, now known as novartis, it is basically a classical precipitation process known to pharmacists under the term via humida paratum vhp this vhp process was employed to prepare ointments containing finely dispersed, precipitated drugs the drug is dissolved in a solvent, allegra online the solvent added to a nonsolvent leading to the precipitation of finely dispersed drug nanocrystals a problem associated with this technology is that the formed nanoparticles need to be stabilized to avoid growth in micrometer crystals in addition, the drug needs to be soluble at least in one solvent this creates problems allegra online for the newly synthesized or discovered drugs, being poorly soluble in water and simultaneously in organic media lyophilization is recommended to preserve the particle size to our knowledge, this technology has not been applied to a product to date amorphous drug nanoparticles nanomorph� depending on the precipitation methodology, drug nanoparticles can allegra online be generated which are in the amorphous state a nice example are carotine nanoparticles in food industry a solution of the carotinoid, together with a surfactant and a digestible oil, are admixed into an appropriate solvent at a specific temperature the solution is mixed with a protective colloid this tranforms the hydrophilic allegra online solvent components into the water phase and the hydrophobic phase of the carotinoid forms a monodisperse phase xray analysis after subsequent lyophilization shows that approximately of the carotinoid is in the amorphous state amorphous precipitation technology is used by the company soliqs and the technology is advertised under the tradename nanomorph� allegra online the preservation of the amorphous state could be achieved successfully for food products to exploit the amorphous technology for pharmaceutical products, the stricter requirements for pharmaceuticals need to be met homogenization methods microfluidizer technology the previous canadian company rtp montreal, now skyepharma canada inc employed the microfluidizer to homogenize drug suspensions the allegra online microfluidizer is a jet stream homogenizer of two fluid streams collied frontally with high velocity up to msec under pressures up to bar there is a turbulant flow, high shear forces, particles collied leading to particle diminution to the nanometer range the high pressure applied and the high streaming velocity of allegra online the lipid can also lead to cavitation additionally, contributing to size diminution the patent describes examples requiring up to passes through the microfluidizer to obtain a nanosuspension sometimes, up to cycles are required when applying the microfluidizer technology this does not pose any problem on the small lab scale, but it is allegra online not production friendly for larger lab scale the dispersion medium is water pistongap homogenization in water dissocubes� in , mueller et al, developed a high pressure homogenization method based on pistongap homogenizers for drug nanosuspension production dispersion medium of the suspensions was water a piston in a large bore cylinder creates pressure allegra online up to bar the suspension is pressed through a very narrow ring gap the gap width is typically in the range of micrometer at pressures between bar there is a high streaming velocity in the gap according to the bernouli equation due to the reduction in diameter from the large bore cylinder allegra online eg cm to the homogenization gap, the dynamic pressure streaming velocity increases and simultaneously decreases the static pressure on the liquid the liquid starts boiling, and gas bubbles occur which subsequently implode, when the suspension leaves the gap and is again under normal pressure cavitation gas bubble formation and implosion lead allegra online to shock waves which cause particle diminution the patent describes cavitation as the reason for the achieved size diminution pistongap homogenizers which can be used for the production of nanosuspensions are eg from the companies apv gaulin, avestin or niro soavi the technology was aquired by skyepharma plc at the end of allegra online the s and employed in its formulation development nanopure technology for oral administration, the drug nanosuspensions themselves are, in most cases, not the final products for patients convenience, the drug nanocrystals should be incorporated in traditional dry dosage form, eg tablets, pellets and capsules an elegant method to obtain a final allegra online formulation directly is the production of nanocrystals in nonaqueous homogenization media drug nanocrystals dispersed in liquid polyethylene glycol peg or oils can be directly filled as drug suspensions into gelatine or hpmc capsules the nonaqueous homogenization technology was established against the teaching that cavitation is the major diminution force in high pressure allegra online homogenization efficient particle diminution could also be obtained in nonaqueous media to prepare tablets or pellets, the dispersion medium of the nanosuspension needs to be removed, ie in general, evaporated evaporation is faster and possible under milder conditions when mixtures of water with water miscible liquids are used, eg waterethanol to allegra online obtain isotonic nanosuspensions for intravenous injection, it is beneficial to homogenize in waterglycerol mixtures the ip owned by pharmasol covers, therefore, waterfree dispersion media eg peg, oils and also water mixtures combination technologies microprecipitation and high shear forces nanoedge the nanoedge technology by the company baxter covers a combination of precipitation and allegra online subsequent application of high energy shear forces, preferentially high pressure homogenization with pistongap homogenizers as outlined in sec , the precipitated particles have a tendancy to grow according to the patent by kipp et al, treatment of a precipitated suspension with energy eg high shear forces avoids particle growth in precipitated suspensions allegra online = annealing process the relative complex patent description can be summarized in a simplified way that the subsequent annealing stabilizes the obtained particle size by precipitation as described in sec , precipitated particles can be amorphous or partially amorphous this implies the risk that during the shelf life of a product, the amorphous particles can recrystalize, leading subsequently to a reduction in oral bioavailability or a change in pharmacokinetics after intravenous injection the annealing process by baxter converts amorphous or partially amorphous particles to completely crystalline material nanopure� xp technology an important criteria for a technology is its scaling up ability and the possibility allegra online to produce on large scale, applying normal production conditions the number of passes through a homogenizer as partially required for the microfluidizer technology is not production friendly pistongap homogenizers sec proved to be more efficient, typically between homogenization cycles are sufficient to obtain a nanosuspension however, it would of course be desirable allegra online to apply even less homogenization cycles, reducing production time, potential product contamination by wearing of the machine and production costs pharma sol developed a new combination process, nanopure xp xtended performance leading to identical particle sizes compared with high pressure homogenization in water sec , but at half the cycle numbers or allegra online less lower particle sizes at identical cycle numbers the process is again a combination technology, a pretreatment step is followd by a high pressure homogenization step, typically performed with a pistongap homogenizer the code for this homogenization technology is h figure [mm] cycle new h cycle old technology fig comparison of the allegra online old homogenization technology homogenization in water, pistongap homogenizer on the right side to the new technology on the left side, presented are the laser diffractometry ld diameters , and volume distribution, coulter ls, beckmancoultergermany with permission after demonstrates the efficiency of method processing a very hard drug material applying the novel h allegra online technology leads to distinctly smaller crystals after just cycles, compared with the old technology of applying cycles application routes and final formulations oral administration most attractive regarding regulatory and commercial aspects is the oral administration route compared with parenteral administration, the regulatory hurdles are much lower in addition, the patient prefers an allegra online oral dosage form, that is why oral products possess the largest percentage of the pharmaceutical market however, for the oral administration route, it is generally necessary to transfer the liquid nanosuspension into a solid dosage form aqueous nanosuspensions can be used as a granulation fluid for producing tablets or as a allegra online wetting agent for pellet production in addition, spray drying can be performed in order to obtain a product which can subsequently be processed to oral products the first nanosuspension product in the market was rapamune�, introduced in by the company wyeth rapamune� is available on the market as oral solution, and alternatively allegra online as tablet the tablet is more userfriendly comparing the oral bioavailabilities of solution and nanocrystal tablet, the bioavailability of the nanocrystals is higher compared with the solution the oral single dose of rapamune� is or mg, the total tablet weight being mg for mg formulation and mg for the mg formulation, allegra online meaning that it contains a very low percentage of its total weight as nanocrystals an important point is that the drug nanocrystals are released from the tablet as ultrafine suspension in the event that crystal aggregation takes place to a pronounced extent, the dissolution velocity, and subsequently, the oral bioavailability of the bsc ii drugs will be reduced therefore, there is an upper limit to load tablets with nanocrystals in case the limit is exceeded and nanocrystals get in contact with each other within the excipient mixture of the tablet, the nanocrystals might fuse to larger crystals under the compression pressure during tablet allegra online production for drugs with a low oral single dose such as sirolimus in rapamune�, incorporation into tablets causes little issues a total nanoparticle load of less than is well below the percentage being critical the second product on the market was emend�, introduced in by the company merck the drug aprepiptant is allegra online for the treatment of emesis single dose is either or mg aprepiptant will only be absorbed in the upper gastrointestinal tract bearing this in mind, nanoparticles proved to be ideal in overcoming this narrow absorption window the large increase in surface area due to nanonization leads to rapid in vivo dissolution, allegra online fast absorption and increased bioavailability, the formulation of a tablet from micronized bulk powder made higher doses necessary, leading to increased side effects the drug nanocrystals are contained within the hard gelatin capsules as pellets aprepiptant was formulated as capsules for it to be user friendly by healthcare providers and patients, and allegra online on the other hand, to make it applicable as pellets via a stomach tube currently, studies are being undertaken to evaluate the change in pharmacokinectics if any between the pellets and the capsules all nanocrystals in these first two products were produced using the pearl mill technology by nanosystemselan the prerequiste allegra online was the bioavailability of sufficient large scale production facilities for the respective product in general, the candidates of first choice for nanosuspension technology are drugs with a relatively low dose it is interesting that drugs such as naproxen are formulated as nanosuspension eg for fast action onset and reduced gastric irritancy, however, allegra online it requires more sophisticated formulation technology to ensure the release of the drug nanocrystals as fine suspension when incorporated in a tablet in a relatively high concentration of a single dose of mg the tablet size weight has to be acceptable for the patient and that a dosing with two tablets allegra online should be avoided, for reasons of patients compliance and marketing purposes alternatively, to aqueous nanosuspensions, nanosuspensions in nonaqueous media can be produced by the nanopure technology pharmasol nanocrystals dispersed in liquid peg or oil can be directly filled into gelatine or hpmc capsules it saves the step of water removal and subsequent allegra online dispersion of the powder in a liquid capsule filling medium the nanopure technology also allows production of nanocrystals in melted peg at � c after solidification of the peg nanosuspension, the drug nanocrystals are fixed and kept seperated in the solid peg matrix the solidified drug nanocrystal containing peg can either allegra online be milled into powders and filled into the capsules, or alternatively, the hot liquid peg nanosuspension can be directly filled into the capsules fig , upper instead of using aqueous nanosuspensions as fluids for the wet granulation process or extrusion of pellet mass, the nanosuspensions can be converted into a dry powder which is subsequently further processed into a tablet or a capsule it also appears attractive to package such powders in sachets for redispersion in water or soft drinks prior to oral food tatse avodart administration spraydrying is the only feasable cost effective way to produce such powders an attractive approach is the production of socalled allegra online compounds as described in the direct compress technology the term compound does not mean a chemical compound in powder technology, compounds are defined as freely flowable granulate powders in the direct compress technology, waterinsoluble polymeric particles eg eudragit rspo, ethyl cellulose are dispersed in the aqueous drug suspension, and lactose is dissolved allegra online the mixture is a freely flowable compound yielded by spraydrying the lactose fig gelatin capsules filled directly with hot liquid pec nanosuspension, solidification takes place in the capsules upper or filling of the capsules with milled solidified peg nanosuspension lower from ref with permissions is responsible for the good flowing properties allegra online the waterinsoluble polymeric particles also contribute to the formation of flowable granules, while at the same time allowing the compound to be compressed in a direct compaction process into tablets the polymers form the matrix structure of the tablet depending on the percentage of the insoluble polymeric particles added, the resulting tablets allegra online may disintegrate fast or present a prolonged release system, a prolonged release of dissolving nanocrystal is desired in the case of high plasma that peaks at very early times short tmuc and a targeted sustained blood level alternatively, the drug nanocrystal compound can be filled into hardgelatinc capsules due to the allegra online presence of lactose and surfactant from the original nanosuspension, the compounds disperse relatively fast in liquids figure shows the dispersion process of a compound after layering it on the surface of water in a beaker as outlined above, efficient release and red is persion of the drug nanocrystals in a fine, nonaggregated allegra online state is a prerequisite for benefiting fully from the drug nanocrystal features parenteral administration intravenous administration is the second frequently investigated route the company baxter, with its technology nanoedge, is presently focusing on intravenous nanosuspensions they investigated itraconazole nanosuspensions intensive it could be nicely shown that the side effects of the allegra online commercial product sporanox� could be distinctly reduced by the administration of a nanosuspension the nephrotoxicity of sporanox� is not caused by the drug, but by the excipient sec sec sec sec sec fig dispersion of a drug nanocrystal compound as a function of time after layering it on the surface of water in a beaker with permission after compound a qua �� at , lactose used for solubilizing the drug, the hydro xy p ro py �� � � d ex tri n the itracon zole nanosuspension was stabilized with tween surfactant being well tolerated intravenously administration of nanosuspsensions into body cavities is also allegra online of great interest, eg to increase the tolerability of the drug, to achieve a local treatment or to have a depot with slow release eg into the blood it could be shown that intraperitonal administration of a nanosuspension was well tolerated, whereas administration of a macro suspension leads to irritancy lazodicarbonamide ada, unpublished data] intraperitonal administration can be used for local treatment or to obtain a depot with prolonged release into the blood interesting therapeutic targets include local inflammations, eg in joints for instance, arthritic joint inflammations are caused by secretion products of activated macrophages an interesting approach is therefore the administration of allegra online a corticoid nanosuspension directly into the joint capsule the drug particles will be phagocytosed, the drug dissolves and reduces the hyperactivity of the macrophages this concept is not new, being adopted by the company boots in the s in an attempt to incorporate the corticoid prednisolone into polymeric nanoparticles made from plagacopolymer allegra online the particle load polymer load required to achieve a therapeutic drug level was being calculated i iowevcr, incubating macrophage cell cultures with the required particle concentration lead to cytotoxicity the concept could not be realized, as it cannot occur with drug nanocrystals since no carrier polymer to required and present producing allegra online parenteral products with drug nanocrystals has to meet higher regulatory hurdles and product quality standards distinctly the produced drug nanosuspensions need to be terminally sterilized or alternatively produced in an aseptic process in principal, sterilization is possible by autoclaving however, the increase in temperature can reduce hydration of steric stabilizers, thus leading allegra online to some aggregation during the sterilization process gamma irradiation is a priori a nonpreferred process by the industry due to the necessary analytics ie proof of absence of toxic irradiation products in addition, it was also observed that irradiation can cause aggregation not by directly interacting with the drug nanocrystals, but allegra online with the stabilizing surfactant irradiation of tarazepide nanosuspension leads to aggregation simultaneously, a decrease in zeta potential also occurred during the irradiation process a decrease in zeta potential, ie electrostatic repulsion, was considered as the cause for the aggregation process it can be concluded that the production of drug nanosuspensions in an allegra online aseptic, controlled process has to be preferred, compared with the terminal sterilization by irradiation the aseptic production process can be validated and documented relatively easy, therefore, being simpler to handle as an irradiation sterilization with accompanied analytics miscellaneous administration routes oral and parenteralintravenous routes are the ones in which developments are allegra online focusing, clearly due to the commercial background and the relation between the development costs for a market product versus its potential annual sales however, drug delivery could also be improved when using drug nanocrystals for pulmonary and ophthalmic adminstration or dermal application poorly soluble drugs could be inhaled as drug nanosuspension the allegra online drug nanosuspension can be nebulized using commercially available nebulizers, disposition in the lungs can be controlled via the size distribution of the generated aerosol droplets compared with microcrystals, the drug is more evenly distributed in the droplets when using a nanosuspension the number of crystals are higher, consequently, the possibility that allegra online one or more drug crystals are present in each droplet is higher it could be shown that nanoparticles possess a prolonged retention time in the eye, most likely due to their adhesive properties from this, poorly soluble drugs could be administered as a nanosuspension however, the major obstacles are the commercial considerations allegra online in many cases, the sales volume do not justify the costs for the development of a new market product this is especially the case when a company has already a drug formulation which might be less efficient, but is already a product on the market the price achievable with an improved allegra online product is not sufficiently high to cover the development costs of this new product an additional major obstacle for the development of such improved products is the cost reduction policy of the healthcare systems worldwide a longer treatment time with a less efficient product might still be less expensive for the healthcare allegra online system than a shorter treatment time with a more efficient, but distinctly more expensive product the same is valid for dermal products sales per product are lower compared with eg oral products, as the dermal market is smaller dermal nanosuspensions are mainly of interest if conventional formulation technology fails or if allegra online it is distinctly less efficient dermal drug nanosuspensions lead to a supersaturated system because of their increased saturation solubility the higher concentration gradient between topical formulation and skin can improve drug penetration into the skin in addition, because of their small size, drug nanocrystals could target the hair follicle by protruding into allegra online the gap around the hairs this was illustrated in solid lipid nanoparticles of a similar size adhesive properties of drug nanocrystals are also an area of interest adherence to the skin reduces the loss of drug to the environmentthird persons this is especially so in the event that highly active compounds allegra online are applied, eg hormones for this reason, the drug estradiole was incorporated into solid lipid nanoparticles to better localize it on the skin nanosuspensions as intermediate products as described above, nanosuspensions can be produced such that nanocrystals appear in final products alternatively, drug nanosuspensions can be used as intermediate product, ie the allegra online drug nanocrystals do not appear in the final product recently, the solemuls� technology was developed to produce drugloaded emulsions for intravenous injection, ie localizing poorly soluble drugs in the interfacial layer of lecithin emulsions the applicability of the technology has been proven for several drugs including amphotericin b, itraconazole ketoconazole, and allegra online carbamazepine among others the drug amphotericin � is on the market as a solution fungizone�, but also in liposomes ambisome� the latter having the benefit of reduced nephrotoxicity liposomes are relatively expensive daily treatment costs approximately eur therefore amphotericin � was incorporated into parenteral emulsions these emulsions can also reduce nephrotoxicity, but allegra online for their production, it was necessary to use organic solvents egg lecithin and amphotericin � were dissolved in an organic solvent, the solvent evaporated and the obtained druglecithin mixture was used to produce an ow emulsion in these emulsions, amphotericin � was located in the interfacial lecithin layer as amphotericin � allegra online is simultaneously poorly soluble in water and in oils there were also attempts to incorporate amphotericin � in the emulsion by simply adding amphotericin � powder to the emulsion and subsequently shaking it however, even shaking for hours with rph was unable to completely dissolve the amphotericin b the reason was simply allegra online due to its low solubility in the water, and the dissolution velocity was also extremely low, ie the process of dissolution and redistribution into the lecithin layer takes too long for it to be used in pharmaceutical production the problem was solved by the solemuls technology, ie simple cohomogenization of oil allegra online droplets and micro crystals for a de novo production, a coarse preemulsion of lecithin stabilized oil droplets in water is prepared, the drug powder is admixed under stirring and the obtained hybrid suspension subsequently homogenized at bar pressure being in the range to be used in pharmaceutical production lines the high streaming allegra online velocities in the homogenization process lead to fast dissolution of the drug microcrystals and the redistribution into the interfacial lecithin layer fig depending on the size of the drug crystals, homogenization cycles are required the number of homogenization cycles can be reduced when adding the drug not as microcrystals, but as allegra online nanocrystals in the form of a nanosuspension a concentrated nanosuspension is prepared eg solid content and added to the preemulsion ideally the nanosuspension is also stabilized by lecithin, ie the same emulsifier for the suspension and the emulsion alternatively, intravenously accepted stabilizers such as tween or poloxamer can be used they are allegra online accepted intravenously without posing any regulatory issues in addition, mixing the emulsion and nanosuspension at a ratio of or higher will dilute the stabilizer concentration used in the nanosuspension by at least a factor of , meaning that in the final product, the nanosuspension surfactant concentration is typically or the question might arise as to why an emulsion should be prepared using a nanosuspension as an intermediate product, when it can administer the nanosuspension itself intravenously lecithin drug fig drug incorporation through various methods in comparison left traditional attempt of shaking or alternatively use of organic solvent right solemuls� process the reason is that allegra online drugloaded parenteral emulsions are already products on the market eg diazepamlipuro, etomidatelipuro, etc, ie in a dosage form with which the regulatory authorities are already familiar with applying fda label flomax the solemuls technology and using lecithinstabilized nanosuspension, the final product will only contain the excipients of an �w emulsion for parenteral nutrition, without allegra online additional excipient plus the drug it is an accepted known system with regard to the excipient status and its perfomance after intravenous injection in contrast, drug nanosuspensions represent a new dosage form not yet present as intravenous formulations on the market registration of a completely new dosage form for a certain administration allegra online route is just more complicated and timely than registration of a product based on an established, known technology perspectives there was a delayed acceptance of the nanocrystal technology in the s pharmaceutical companies tried to solve their formulation problems with the traditional formulation approaches however, the increasing number of drugs having allegra online a very low solubility, and not able to be formulated with these traditional formulation approaches, lead to a broad acceptance of the drug nanocrystal technology this is clearly reflected in the increasing number of licensing agreements between companies holding nanocrystal ip and a number of medium and large pharmaceutical companies the smartness allegra online of the technology is that it can be universally applied to practically any drug identical to micronization, it is a universal formulation principle, but limited to bsc drugs class ii the time between the beginning of intensive research in the drug nanocrystal technology and the first products on the market was allegra online relatively short, about one decade the value of a formulation principle or technology can be clearly judged by looking at the number of products on the market, in the clinical phases, andor the time of entry into the market based on these criteria, the drug nanocrystal technology is a successful emerging technology allegra online meanwhile, big pharma also realized the drug nanocrystal value in combination with the further increasing number of poorly soluble drugs, a distinct increase in drug nanocrystalbased products on the market can be expected in many cases, oral products will dominate because of the market share, higher sales volumes and less regulatory allegra online hurdles and quality requirements, compared with parenteral products references speiser pp poorly soluble drugs, a challenge in drug delivery, in muller rh, benita s and bohm � eds, emulsions and nanosuspensions for the formulation of poorly soluble drugs, medpharm scientific publishers stuttgart meriskoliversidge e nanocrystals resolving pharmaceutical formulation issues associated with poorly allegra online watersoluble compounds in particles, marcel dekker orlando bangham ad and haydon da ultrastructure of membranes biomolecular organization brit med bull anger s phd thesis, in phd thesis pharmaceutical technology freie universitat berlin mtiller rh, luck m and kreuter j arzneistofftragerpartikel fur die gewebsspezifische arzneistoffapplikation europaische patentschrift, pctep kreuter j, kharkevich rn allegra online and ivanov da passage of peptides through the blood brain barrier with colloidal polymer particles nanoparticles brain res gu chonghui gdjw estimating the relative stability of polymorphs and hydrates from heats of solution and solubility data j pharm sci hancock � and bruno p what is the true solubility advantage for amorphous pharmaceuticals?