Enhanced Dissolution of Ursodeoxycholic Acid from the Solid Dispersion

Solid dispersions of a very slightly water-solubte drug, ursodeoxycholic acid (UDCA), were prepared using urea, mannitol, and PEG 6000 as a carrier, and the solubility of UDCA was determined in water-ethanol (1:1) mixed solvent as a function of UDCA-carrier ratio. The solubility of UDCA was slightly improved when urea or PEG 6000 was used as a carrier. The powder x-ray diffraction measurements revealed that UDCA did not exist in the crystalline state in the solid dispersions. Differential scanning calorimetry (DSC) studies showed that UDCA was able to dissolve in the melt of urea, mannitol, and PEG 6000. The effect of carriers of solid dispersions on the UDCA dissolution rate was examined. The dissolution rate of UDCA was markedly increased from the solid dispersions of urea, PEG 6000, and mannitol, respectively.     

Enhanced Dissolution of Ibuprofen Using Solid Dispersion with Polyethylene Glycol 20000

To improve its dissolution, ibuprofen solid dispersions (SDs) were prepared in a relatively easy and simple manner, characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR), and evaluated for solubility and in vitro drug release. Loss of individual surface properties during melting and re-solidification as revealed by SEM micrographs indicated the formation of effective SDs. Absence or shifting toward the lower melting temperature of the drug peak in SDs in DSC study indicated the possibilities of drug–polymer interactions. FTIR spectra showed the presence of drug crystalline in SDs. The effect of improved dissolution on the oral absorption of ibuprofen in rats was also studied. Quicker release of ibuprofen from SDs in rat intestine resulted in a significant increase in AUC and C_max, and a significant decrease in T_max over pure ibuprofen. Preliminary results from this study suggested that the preparation of fast dissolving ibuprofen SDs by low-temperature melting method using polyethylene glycol 20000 as a meltable hydrophilic polymer carrier could be a promising approach to improve solubility, dissolution, and absorption rate of ibuprofen.     

Investigation of Dissolution Enhancement of Itraconazole by Solid Dispersion in Superdisintegrants

Solid dispersions of itraconazole (ITR) in lactose, microcrystalline cellulose (MCC), and three superdisintegrants (Primogel, Kollidon CL, and Ac-Di-Sol) and their formulation into tablets were investigated with an objective of enhancing the dissolution rate of ITR from tablet formulations. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) were used to characterize the dispersions. A marked enhancement in the dissolution rate of ITR was observed with all the excipients. The order for the excipients to enhance the dissolution rate was Ac-Di-Sol > Kollidon CL > Primogel > MCC > lactose. Solid dispersions in superdisintegrants gave much higher rates of dissolution than the dispersions in other excipients. Ac-Di-Sol gave the most improvement (28-fold) in the dissolution rate of ITR at a 1:1 drug: excipient ratio. Solid dispersions in superdisintegrants could be formulated into tablets. These tablets, apart from fulfilling all official and other specifications, exhibited higher rates of dissolution and dissolution efficiency (DE) values. XRD indicated the presence of ITR in amorphous form in the dispersions. DSC indicated a weak interaction between ITR and the excipients. Micronization and conversion of the drug into the amorphous form and the fast disintegrating and dispersing action of the superdisintegrants contribute to the enhancement of the dissolution rate of ITR from its solid dispersions in superdisintegrants and their corresponding tablet formulations.     

Enhancement of Dissolution and Bioavailability of Piroxicam in Solid Dispersion Systems

Solid dispersion systems of water-insoluble piroxicam in polyethylene glycol (PEG) 4000 and in urea were prepared by fusion and solvent methods and were characterized in this study. The in vitro dissolution studies showed that the dispersion systems containing piroxicam and PEG4000 or urea gave faster dissolution than the corresponding simple mixtures. The differential scanning calorimetry (DSC) study indicated that the piroxicam-PEG system prepared by the fusion method is a solid dispersion, while the piroxicam-urea system prepared by the solvent method is likely to be a solid solution of piroxicam in urea. The storage testings showed that all dispersions were stable, except that uptake of water during storage may occur in the PEG system. A single-dose study with rabbits showed that the dispersion systems provided statistically significant to a higher extent and rate of bioavailability than the corresponding physical mixture (p < 0.05).     

Dissolution Rates of Carbamazepine and Nitrazepam Utilizing Sugar Solid Dispersion System

Abstract

The dissolution of carbamazepine and nitrazepam from Its solid dispersions using anhydrous lactose, mannitol, galactose, PEG 6000 and coprecipitate using polyvinylpyrrolidone (PVP) 40,000 was investigated. The dissolution process of capsules containing either carbamazepine or nitrazepam as solid dispersion or coprecipitate followed an apparent first order process. The combination of carbamazepine with sugars (mannitol, lactose, and galactose) caused, in every case, an increase in the dissolution rate of the drug. Carbamazepine-PVP coprecipitate gave the higher dissolution rate than that of the solid dispersions with sugars and PEG 6000. Nitrazepam-lactose system gave higher dissolution rate than the other dispersions and coprecipitate. This enhancement in dissolution rate was much more obvious for the solid dispersions and coprecipitate than for the physical mixtures.     

Increasing the Dissolution Rate of some Benzothiadiazine Derivatives by Solid and Liquid Dispersion Techniques

Abstract

Dissolution rates of water-insoluble drugs such as Chlorothiazide, Hydrochlorothiazide, Flumethiazide and Cyclopenthiazide were markedly increased when dispersed in polyethylene glycol 6000. The increased dissolution rate was believed to be attributed to the molecular and for the colloidal dispersion of the drug in the matrix of PEG 6000. Bendroflumethiazide and Methylclothiazide were found to be decomposed by either of dispersion techniques.     

Increasing the Dissolution Rate of some Benzothiadiazine Derivatives by Solid and Liquid Dispersion Techniques

Dissolution rates of water-insoluble drugs such as Chlorothiazide, Hydrochlorothiazide, Flumethiazide and Cyclopenthiazide were markedly increased when dispersed in polyethylene glycol 6000. The increased dissolution rate was believed to be attributed to the molecular and for the colloidal dispersion of the drug in the matrix of PEG 6000. Bendroflumethiazide and Methylclothiazide were found to be decomposed by either of dispersion techniques.     

Improvement of Aqueous Solubility and Dissolution Kinetics of Canrenone by Solid Dispersion in Sucroester

Abstract

Sucroester 7 (sucrose di-stearate), by melting and rapid cooling, gives a product with a glassy appearance that corresponds to a low physical stability state or a high solubility power. This property, added to its surfactive characteristics, enables considerable improvement not only in aqueous solubility, but, to a greater degree, in the dissolution kinetics of canrenone. This result should lead to a reduction in the long lag time observed after oral administration before the diuretic effect of the product.     

Preparation of a Solid Dispersion by a Dropping Methodto Improve the Rate of Dissolution of Meloxicam

Application of a solid dispersion system is one of the methods used to increase the bioavailability of poorly water-soluble drugs. Adaptation of the dropping method from the chemical industry as a formulation procedure may help the scaling-up process and simplify the formulation of poorly water-soluble compounds. Meloxicam (ME), a nonsteroidal anti-inflammatory drug that is poorly soluble in water, and polyethylene glycol (PEG) 4000, a water-soluble carrier, were formulated by using a dropping method in an attempt to improve the dissolution of ME. Pure ME and physical mixtures and tablets of ME–PEG 4000 (1:3 ratio) were compared as regards their dissolution with samples formulated by the dropping method. The results revealed that the round particles (solid drops) exhibited a higher dissolution rate than those of the physical mixtures, tablets, and pure ME. Self-modeling curve resolution (SMCR) as a chemometric method was used to evaluate X-ray powder diffractometry (XRPD) data. The results demonstrated the presence of a new crystalline phase in the solid dispersion, which can help the fast and quantitative dissolution from the solid drops. The round particles can be adapted to individual therapy by using a distributor.     

Effect of Particle Size on the Dissolution Rate of Monophenylbutazone Solid Dispersion in Presence of Certain Additives

Abstract

Monophenylbutazone is a very sparingly soluble drug. The effect of particle size on the dissolution characteristics of monophenylbutazone in a dissolution medium of 0.1 N hydrochloric acid and 0.1 N hydrochloric acid to which was added 0.005% Tween 80, was carried out. The enhancement of the dissolution rate of the medicament was attained by formulating the drug in both solid dispersion and physical mixture using urea and polyethylene glycol 4000 as carriers. A comparative dissolution behaviour of the medicament in different solid dispersion and physical mixture ratios were investigated at particle, size of < 63 μ. Drug-urea solid dispersion of a ratio 5:95% produced the highest dissolution rate.     

Batch Variation of Magnesium Stearate and its Effect on the Dissolution Rate of Salicylic Acid from Solid Dosage Forms

The effects of different batches of magnesium stearate on the release of salicylic acid from capsules and from a compacted formulation have been investigated. The results indicate that retardation of salicylic acid release becomes independent of the particle size of magnesium stearate when the blending of the two substances prior to encapsulation or compaction is prolonged for a sufficient time.

Variation in the release rates observed after prolonged blending times have been shown to exhibit a rank order correlation with the different hydrophobicities of the batches of magnesium stearate as indicated by the results of contact angle measurements on drops of dissolution medium on compacts of this lubricant.

Determination of the surface tension of an aqueous extract of each batch of lubricant has indicated that water-soluble, surface-active impurities may be responsible for this apparent variation in the degree of hydrophobicity and hence for the change in the release rate of salicylic acid from solid dosage forms when they are manufactured with different batches of magnesium stearate.     

Dissolution of Omeprazole from Delayed-Release Solid Oral Dosage Forms

The evaluation of the biopharmaceutical quality of omeprazole enteric-coated products (granules in capsules) with respect to its dissolution characteristics is not specifically regulated in any of the most common official pharmacopoeia. USP 23 includes a general monograph for enteric-coated products. This paper reports the evaluation of the medium pH effect on the dissolution rates of omeprazole from four omeprazole-containing products of different manufacturers. It is concluded that the USP 23 recommended dissolution procedure for enteric-coated products is not suitable due to the degradation of omeprazole under such conditions. Furthermore, the medium with pH 8.0 showed different dissolution rates not observed at pH 7.4, allowing discrimination between products of different manufacturers.     

固体颗粒的分散

详细阐述了固体颗粒分散的原理及实践。指出了颗粒分散研究所存在的问题和解决的办法。     

Dissolution of Nalidixic Acid Solid Dispersions: Systems of NAL-Inclusion and Linear Polymeric Compounds

The solubility and dissolution rate enhancement of nalidixic acid powder, applying solid dispersion technique, with inclusion and linear polymeric compounds were studied. At 100 g/L carrier concentration, the increase in drug solubility was 3.3, 2.0, 1.4 and 1.1 times that of the powdered drug for urea, PEG 4000, PEG 6000 and PVP, respectively. The increase in carrier ratio enhanced the drug dissolution. At four fold carrier concentrations, the amount dissoluted after one hour was 50, 55 mg/L for samples prepared by fusion with urea and PEG 6000, respectively. The coprecipitation with FTP dissoluted 65 mg/L of nalidixic acid after one hour compared to only 27.5 mg/L of powdered drug alone.     

Dissolution OP Nalidixic Acid Solid Dispersions 1. Nal-Hydrotropic salts and NAL-Hyrj systems

The effect of solid dispersion techniques on the dissolution rate of nalidixic acid powder was investigated.

The thermodynanic parameters of all tested systems revealed a spontaneous reaction with no complex affinity to the drug.

Hexamine and sodium citrate showed very powerful solubilizing capacity towards NAL powder.

For piperazine citrate in spite of its low interaction with NAL in the aqueous phase, it proved to be efficient carrier in the solid dispersion system. Hyrj 59 caused the greatest enhancement in NAL dissolution rate of all carriers examined. After 5 minutes, the RDR of the four-fold NAL-HyrJ 59 co-precipitate system was 16.5 times the untreated drug.     

Dissolution of Nalidixic Acid Solid Dispersions: Systems of NAL-Inclusion and Linear Polymeric Compounds

Abstract

The solubility and dissolution rate enhancement of nalidixic acid powder, applying solid dispersion technique, with inclusion and linear polymeric compounds were studied. At 100 g/L carrier concentration, the increase in drug solubility was 3.3, 2.0, 1.4 and 1.1 times that of the powdered drug for urea, PEG 4000, PEG 6000 and PVP, respectively. The increase in carrier ratio enhanced the drug dissolution. At four fold carrier concentrations, the amount dissoluted after one hour was 50, 55 mg/L for samples prepared by fusion with urea and PEG 6000, respectively. The coprecipitation with FTP dissoluted 65 mg/L of nalidixic acid after one hour compared to only 27.5 mg/L of powdered drug alone.     

Characterization and Dissolution Study of Oxodipine from Solid Binary Systems

Thennomicroscopy and differential scanning calorimetry were employed to characterize solid binary systems prepared with oxodipine and PEG 6000, 2-hydroxypropyl-β-cyclodextrin or mannitol. DSC curves did not allow to diferentiate physical mixtures from solid dispersions. Thennomicroscopy revealed the interactions that can be produced between drug and each carrier, due to heat contribution, when the physical mixtures were observed; also this thermal technique permited us to ascertain the composition of particles that constitute the solid dispersions. Dissolution studies showed that the amelioration obtained in oxodipine dissolution from physical mixtures was due to the dessagregant action of the carriers, which obtained an increase of the drug surface in contact with the dissolution medium. The proportions and carrier nature influence the oxodipine dissolution, fundamentally from solid dispersions, where the interaction drug/carrier is stronger than in physical mixtures.     

Dissolution Behavior of Griseofulvin Solid Dispersions Using Polyethylene Glycol, Talc, and Their Combination as Dispersion Carriers

Griseofulvin solid dispersions were prepared using polyethylene glycol 6000 (PEG), talc, and their combination as carriers by the solvent method. The dissolution of griseofulvin from these dispersions was studied. It was found that in these carriers the drug dissolution rate was a function of drug loading. The dissolution rate from dispersions prepared using PEG was similar to that from PEG/talc dispersions, especially at a low percentage of drug loading. Dispersions of PEG and PEG/talc provided dissolution rates faster than those from dispersions of talc. The incorporation of talc in PEG yielded dispersions with properties of less tackiness and ease for handling. Dissolution kinetics, based on the Hixson-Crowell equation, was used to determine the characteristics of griseofulvin particles in dispersions. Linear relationships were obtained for PEG and PEG/talc dispersions that indicated the presence of a uniformly sized monoparticulate system, whereas deviation from linearity was observed for talc dispersions. This appeared to be a multiparticulate system in which particles were present as free form and adsorbed form on the surface of talc.     

Solubility and Dissolution of Etoposide from Solid Dispersions of PEG 8000

The Solubility and dissolution of etoposide from solid dispersion of PEG 8000, prepared by the fusion method, were investigated. Stability studies revealed that the etoposide was stable in water for three days at 37 ± 0.5°C alone and as a physical mixture with PEG 8000. However, nearly 5% decomposition was oberved in aqueous solutions made from solid dispersions. TLC, IR and HPLC studies showed both the drug and carrier were stable during the fusion process. Aqueous solubility of etoposide from solid dispersions with etoposide: PEG 8000 ratios of 1:5, 1:10, 1:20, 1:30 and 1:40, was studied at 37 ± 0.5°C, and found to be significantly higher than that of etoposide alone or from its physical mixtures with PEG 8000. These dispersions increased the solubility of etoposide by 32.3%, 96.8%, 133.5%, 280.7% and 326.6% respectively compared to that of etoposide alone, whereas only 1:40 etoposide: PEG 8000 physical mixture demonstrated a significant increase in etoposide solubility (16.1%). Dissolution studies, on the solid dispersions in water at 37 ± 0.5°C, revealed a marked increase in the dissolution rate of etoposide from 1:20, 1:30 and 1:40 solid dispersions with 100% drug dissolving within 1 minute; dissolution time for 1:5 and 1:10 dispersions, and all physical mixtures was 3 minutes while etoposide alone required 30 minutes for complete drug dissolution. The melting behavior of the etoposide-PEG 8000 mixtures and subsequent thermal analysis of the melts suggested that the increase of solubility of etoposide was mostly due to the formation of a solid solution of etoposide in PEG 8000.     

Controlled-Release Matrix of Acetaminophen-Ethylcellulose Solid Dispersion

In this study ethylcellulose was evaluated as a carrier for preparation of prolonged release acetaminophen tablets. Solid dispersions containing three levels of ethylcellulose and acetaminophen (1:3; 1:1; 3:1) were prepared by the solvent method. Also physical mixtures at the same level of ethylcellulose and acetaminophen were prepared. Systems composed of solid dispersion or physical mixture containing the equivalent weight of 50 mg acetaminophen, Lactose fast-flo as diluent and 1% magnesium stearate as lubricant were compressed into tablets and tested for dissolution. The dissolution data showed that the drug release decreased as the level of ethylcellulose increased in the solid dispersion formulations. The drug release from tablets prepared with solid dispersion followed the diffusion controlled model for inert porous matrix, while the drug release from tablets prepared with physical mixture followed the first-order kinetic model.