Stabilizer choice for rapid dissolving high potency itraconazole particles formed by evaporative precipitation into aqueous solution

Sinswat, Prapasri; Gao, Xiaoxia; Yacamán, Miguel José; Williams, Robert O.; Johnston, Keith P.

doi:10.1016/j.ijpharm.2005.06.027

Cited by 50 publications

(34 citation statements)

References 33 publications

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“…Precipitation of the dissolved PTX was delayed, however, in the presence of poloxamer (Tables 2, 3), confirming the fact that this polymer effectively stabilizes nanodispersed systems. 17) On the other hand, the type of lecithin influenced the solubility of co-lyophilized PTX in the presence of poloxamer. When the results obtained in solutions prepared with isotonic glycerol as a solvent are considered, the solubility of PTX in the egg lecithin-poloxamer and soya lecithin-poloxamer systems was 36 mg/ 100 ml and 1.6 mg/100 ml, respectively (Table 2).…”

Section: Resultsmentioning

confidence: 99%

Paclitaxel Solubility in Aqueous Dispersions and Mixed Micellar Solutions of Lecithin

Sznitowska

Klunder

Płaczek

2008

CHEMICAL & PHARMACEUTICAL BULLETIN

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Paclitaxel (PTX) is a very effective antineoplastic agent used to treat a variety of tumors. It was discovered in the 1960s in a screening study by the National Cancer Institute designed to develop new natural substances with anticancer activity. PTX brought much hope to people with cancer, but its poor solubility in water and insufficient supply have slowed clinical studies of the drug. 1)After much investigation, an appropriate PTX formulation containing Cremophor EL (ethoxylated castor oil) and dehydrated ethanol (1 : 1 v/v) and suitable for intravenous infusion was found. The Bristol-Myers Squibb Company owned the first patent on a PTX formulation that was introduced to the market in 1993 under the name Taxol. At present, as the patent has expired, many generic products are on the market, all containing Cremophor EL. This solubilizing agent ensures sufficient drug solubility and stability but evokes many severe side effects.2,3) Cremophor EL is responsible for acute hypersensitivity reactions that affect about 30% of patients. It also contributes to peripheral neuropathy and leaches the plasticizers from polyvinyl chloride (PVC) bags and infusion sets. As a result, PTX solutions must be prepared and administered in non-PVC infusion systems with in-line filtration, and pre-medication must be given to patients. These issues have provoked considerable interest in the development of taxanes with improved aqueous solubility and in formulations devoid of Cremophor EL.Increased solubility of the drug, which is necessary for intravenous delivery, can be achieved by, for example, using co-solvents or preparing an emulsion, 1,4) by modification of the PTX molecule into prodrugs 5,6) or analogs, 7,8) and by preparing liposomes 4) or micelles. 9) However, none of these formulations has been introduced to clinical practice yet, due to the lack of sufficient biocompatibility to meet the requirements of intravenous preparations. However, in 2005 the FDA (Food and Drug Administration) approved Abraxane for injection (Abraxis BioScience), the first alternative to the Cremophor-containing preparation. It is a nanosuspension of PTX conjugated with human albumin. 10) Despite its better clinical profile, Abraxane is generally not replacing Taxol in oncological practice, mostly due to its high cost. Hence, further research into alternative formulations suitable for parenteral infusion is justified.The aim of our study was to develop a new PTX formulation using excipients that are already in use for parenteral administration. Since PTX must be given to the patients as an infusion, the choice of suitable carriers is very limited. Unfortunately, neither submicron, lecithin-based emulsions nor liposomes ensure appropriate PTX solubility and stability. For example, the solubility of PTX in soybean oil, which is used in parenteral emulsions, is about 180 mg/100 g, and this allows preparation of an emulsion with PTX at a concentration of only 18 mg/100 ml, if the oil content in the emulsion is 10%. PTX is soluble in some types of emulsi...

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Section: Resultsmentioning

confidence: 99%

Paclitaxel Solubility in Aqueous Dispersions and Mixed Micellar Solutions of Lecithin

Sznitowska

Klunder

Płaczek

2008

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…On the other hand, HLB value of the stabilizers can be ranked as SLS>PVP>tween>HPMC. 31,32 The use of SLS, PVP and tween produced moderate effects on the particle size of the agglomerates when MA and EA were employed, but in case of IPA poor effects was observed. In fact, in the case of IPA, very similar particle sizes were observed in relation to pure water if SLS, PVP and tween ( Figure 1) were applied.…”

Section: Eqmentioning

confidence: 99%

Agglomeration of Celecoxib by Quasi Emulsion Solvent Diffusion Method: Effect of Stabilizer

Maghsoodi

Nokhodchi

2016

Adv Pharm Bull

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“…These include solid dispersions composed of solid state microfines or molecular dispersions, water-soluble cyclodextrin complexes and self-emulsifying drug delivery systems using diverse surfactants. 1,2) The principle limitation of all these approaches is that the drug needs to have certain physicochemical properties. For example, sufficient solubility in oils or surfactants is needed for self-emulsifying drug delivery systems and the proper molecular size is essential for synthesizing a complex with cyclodextrin.…”

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confidence: 99%

Effect of Process Parameters on Formation and Aggregation of Nanoparticles Prepared with a Shirasu Porous Glass Membrane

Seo

Kim

et al. 2015

CHEMICAL & PHARMACEUTICAL BULLETIN

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The objectives of this study were to prepare itraconazole (ITZ) nanoparticles using a Shirasu porous glass (SPG) membrane and to characterize the effects of diverse preparation parameters on the physical stability of nanoparticles. SPG membrane technology was used for the antisolvent precipitation method. The preparation of nanoparticles was carried out over a wide range of continuous-phase factors (type of surfactant, surfactant concentration), dispersed-phase factors (solvent type, solvent volume used to dissolve ITZ), and technical factors (pressure, membrane pore size, stirring speed in the continuous phase, temperature). Improved physical stability of nanoparticles was observed when surfactant with a lower molecular weight and higher hydrophilic segment ratio was used. The water miscibility of the solvent also had an effect on the physical stability. N,N-Dimethylacetamide contributed to creating a well-rounded shape and narrow size distribution due to high miscibility. Concentration of the surfactant and solvent volume used for dissolving ITZ were related to instability of nanoparticles, resulting from depletion attraction and Ostwald ripening. In addition to these factors, technical factors changed the environment surrounding ITZ nanoparticles, such as the physicochemical equilibrium between surfactant and ITZ nanoparticles. Therefore, the appropriate continuous-phase factors, dispersed-phase factors, and technical factors should be maintained for stabilizing ITZ nanoparticles.Key words Shirasu porous glass membrane; antisolvent precipitation; nanoparticle; itraconazole; physical stability Oral administration of poorly water-soluble drugs often leads to many problems in drug research and development. The aqueous solubility of a drug is an important factor for its dissolution rate. Poorly soluble compounds tend to be eliminated from the gastrointestinal (GI) tract before they have had opportunity to be absorbed into the circulation, and the low dissolution rate arising from low solubility results in low bioavailability. In such cases, dose escalation often causes topical toxicity in the GI tract and reduces patient compliance, which would be required for reaching therapeutic concentrations in the blood. 1)There have been many attempts to increase bioavailability and dissolution rate of poorly water-soluble drugs. These include solid dispersions composed of solid state microfines or molecular dispersions, water-soluble cyclodextrin complexes and self-emulsifying drug delivery systems using diverse surfactants.1,2) The principle limitation of all these approaches is that the drug needs to have certain physicochemical properties. For example, sufficient solubility in oils or surfactants is needed for self-emulsifying drug delivery systems and the proper molecular size is essential for synthesizing a complex with cyclodextrin. In addition, the use of solubilizing excipients in drug solubilization is limited because of their toxicity or volume of formulation. Because of these limitations, there are the relativel...

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Stabilizer choice for rapid dissolving high potency itraconazole particles formed by evaporative precipitation into aqueous solution

Cited by 50 publications

References 33 publications

Paclitaxel Solubility in Aqueous Dispersions and Mixed Micellar Solutions of Lecithin

Paclitaxel Solubility in Aqueous Dispersions and Mixed Micellar Solutions of Lecithin

Agglomeration of Celecoxib by Quasi Emulsion Solvent Diffusion Method: Effect of Stabilizer

Effect of Process Parameters on Formation and Aggregation of Nanoparticles Prepared with a Shirasu Porous Glass Membrane

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