Comparative Dissolution Study Research Articles

Comparative Dissolution Studies for Mefenamic Acid-Polyethylene Glycol Solid Dispersion Systems and Tablets

ABSTRACTThe purpose of this study was to enhance the dissolution of mefenamic acid (MFA) through the formation of solid dispersion systems, and to compare the dissolution of the unformulated dispersions with those of formulated dispersions in tablets. Solid dispersions of MFA were prepared in polyethylene glycol 3350 (PEG) as a binary system, and PEG and Tween 20 (TW) as a ternary system by the melt method. The dispersions were characterized by dissolution, scanning electron microscopy, and powder x-ray diffraction studies. A decrease in MFA composition in the binary dispersion systems from 50 to 5% w/w resulted in a 50% increase in the dissolution rate during the period of study, and this was threefold higher than that of pure MFA. Incorporation of TW in the preparation of ternary dispersion systems resulted in a further increase in MFA dissolution. A sevenfold increase in MFA dissolution was observed when the ternary system composition was MFA/PEG/TW 4.7:93:2.3 (% w/w). Scanning electron microscopy and x-ray diffraction pictures showed an increase in size and decrease in crystallinity of the dispersions, respectively. Compression of the dispersions into tablets did not have any effect on the dissolution of the drug from the dispersions. Compression of pure MFA and Avicel PH 101, which was used as a diluent and disintegrant, resulted in a threefold increase in dissolution. However, the dissolution of the uncompressed mixture was identical to that of pure MFA. Thus, further processing of the solid dispersions into tablets did not decrease the rate of dissolution of the drug in the dispersions. This may be very important in the formulation of solid dispersions as tablets, which could lead to a reduction in the dose of practically water-insoluble drugs

Comparative dissolution studies of rectal formulations using the basket, the paddle and the flow-through methods: II. Ibuprofen in suppositories of both hydrophilic and lipophilic types

Abstract The applicabilities of the paddle, basket and flow-through methods have been investigated for four different rectal compositions of both hydrophilic and lipophilic types containing ibuprofen. The formulations were studied with respect to in vitro dissolution rate and behaviour in the different apparatus. The reproducibility of the three techniques was also tested by using a hydrophilic and a lipophilic composition. None of the techniques appeared to be more applicable than the others for the compositions tested, though the dissolving suppositories are less sensitive to the technique used than the melting ones. It has been found necessary to consider the behaviour of the product, with regard to its composition and the in vitro method used, when judging the applicability of a dissolution test for a rectal dosage system. Comparison to our previous data on paracetamol also shows that the physical-chemical properties of the drug substance are of great importance, and must be considered, when the judgement of applicability is made.

Ursodeoxycholic acid: Effects of formulation on in vitro dissolution

A new rapid-dissolving granule formulation of ursodeoxycholic acid has been developed which achieves an increased ursodeoxycholic acid solubility in vitro. Granules were prepared with excipients designed to accelerate the disintegration rate and improve the wetting of ursodeoxycholic acid and therefore solubility in vivo. The granules contained polyvinylpyrrolidone, lactose and croscarmallose sodium together with ursodeoxycholic acid (100 or 250 mg) in size ‘0’ hard gelatin capsules and their dissolution characteristics were assessed, at pH 7.2, using an in vitro dissolution method based on the USP XXII (apparatus 2). Detection of dissolved ursodeoxycholic acid was achieved with a specific enzyme assay based on 3α-hydroxysteroid dehydrogenase (EC 1.1.1.50). The 100 mg rapid-dissolving granule formulation was found to release at least 90% of the ursodeoxycholic acid into solution at 15 min, increasing to 100% after 60 min, while the 250 mg rapid-dissolving granule formulation was found to release 76 and 86% of the ursodeoxycholic acid at 15 and 60 min, respectively. A dissolution study carried out using 250 mg capsules containing unformulated ursodeoxycholic acid showed that physical form greatly affected solubility. The sodium salt of ursodeoxycholic acid was soluble in dissolution media, 97% after 15 min, whereas the pharmaceutically approved free acid reached only 20% dissolution in the crystalline form and 66% dissolution in the micronised form, increasing to 38 and 83%, respectively, after 60 min. A comparative dissolution study, with volume corrections to dissolution media to take account of potency, was carried out using two commercial preparations of ursodeoxycholic acid, Destolit ® and Actigall ®. These preparations were found to release 45.8 and 27.5% ursodeoxycholic acid at 15 min increasing to 89 and 39% at 60 min, respectively, and were therefore all potentially less effective than the 250 mg rapid-dissolving granule formulation in vivo. The medical implications of variable ursodeoxycholic acid solubility achieved with different formulations are discussed.

Comparison of Three Dissolution Devices for Evaluating Drug Release

AbstractThe dissolution studies are usually conducted on “official” USP dissolution devices or “non-official” dissolution devices like the Rotating Bottle Apparatus. The recent introduction of the Bio-Dis® Tester exacerbates a difficult situation : no comparative dissolution studies have been done regarding the results for a drug and/or dosage form using these three different instruments. The purpose of this investigation was to evaluate and compare three dissolution devices - USP XXI Dissolution Apparatus II, Rotating Bottle Apparatus, and Bio-Dis® Tester -taking into account pertinent factors that can affect dissolution. Dissolution profiles were obtained for two drugs - theophylline and phenylpropanolamine HCI. Three dosage forms of each drug were evaluated at different agitation intensities using two different dissolution media (simulated gastric fluid and simulated intestinal fluid) on all three dissolution devices. Various advantages/limitations for each device were observed depending on the drug, d...

Design and Evaluation of a Rotating Basket-Paddle Dissolution Apparatus

The rotating basket-paddle dissolution apparatus is a combination of the USP/NF rotating basket and rotating paddle. A comparative dissolution study was performed utilizing this new apparatus and the two USP/NF apparatus at various stirring speeds using non-disintegrating oxalic acid tablets and disintegrating aspirin tablets. The amount of drug released using the new apparatus was significantly higher than the rotating basket but significantly lower than the rotating paddle at each of the stirring speeds studied. The results obtained using this new apparatus were highly reproducible compared to the USP/NF apparatus.

Comparative dissolution characteristics of bropirimine-β-cyclodextrin inclusion complex and its solid dispersion with PEG 6000

An inclusion complex of bropirimine (ABPP) with β-cyclodextrin (βCD) and its solid dispersion with polyethylene glycol 6000 (PEG 6000) were prepared by the coprecipitation method. Comparative dissolution studies revealed that the solid complex exhibited a markedly faster dissolution rate compared to the PEG 6000 solid dispersions and physical mixtures in water and phosphate buffer (pH 7.4). However, the dissolution of all the test preparations was enhanced to almost the same extent in 0.1 N HCl. 1H-NMR was employed to confirm the inclusion of the drug within the β-CD cavity. The high solubility and instant release of the drug were maintained upon ageing of the solid complex for 1 year, while the release of the solid dispersions decreased. TLC investigations proved that this decrease in the release rate was not due to drug degradation.

Comparative dissolution of commercuially available hydroxyzine hydrochloride tablets

AbstractA comparative dissolution study was conducted on commercially available hydroxyzine hydrochloride tablets using USP Apparatus 2 (Paddle Method) at 50 rpm and two dissolution media: Water and Simulated Intestinal Fluid (SIF) and the USP recommended method employing the disintegration apparatus. The dissolution characteristics of 22 samples of hydroxyzine hydrochloride tablets representing four dosage levels and seven manufacturers were profiled.The study illustrated that the Modified Disintegration apparatus is not able to distinguish slow dissolving formulations from fast dissolving formulation and, consequently, does not provide assurance of bioequivalence and does not perform as an adequate manufacturing control to insure lot to lot uniformity.

Particle size dependency of dissolution rate and human bioavailability of phenytoin in powders and phenytoin-polyethylene glycol solid dispersions.

Commercially available phenytoin crystals were fractionated by passing them through 44-350 μm sieves, then blended with diluents to prepare phenytoin-diluent physical mixture or made into solid dispersions with polyethylene glycol 4000 (PEG 4000). Dissolution studies of phenytoin in artificial gastric juice suggested that less than 1 to 10 ratio of phenytoin to PEG 4000 was required to disperse amorphous phenytoin completely in the carrier. A comparative dissolution study of various sizes of phenytoin crystals revealed the existence of a critical particle size between 74-149 μm, but phenytoin in solid dispersions showed far faster dissolution and higher solubility than any of the particle fractions. A three-way cross-over study was carried out for phenytoin crystals of particle size 44-53 μm, phenytoin-diluent physical mixture and the phenytoin solid dispersion in five healthy human volunteers. The solid dispersion gave the highest bioavailability of phenytoin, followed by the physical mixture. Thus, phenytoin solid dispersion in PEG 4000 appears to have the clinical advantages of quick release and excellent bioavailability. It also appears that there is a critical particle size for dissolution of phenytoin from powders in vitro. The phenytoin solid dispersion gave a larger bioavailability than crystals below the critical size in vivo.

In Vitro Release of Hydrochlorothiazide from Capsule Formulations

AbstractFive different hydrochlorothiazide (50mg. per capsule) capsule formulations were prepared with one of the following diluents: corn starch, dibasic calcium phosphate, lactose, microcrystalllne cellulose, or sodium carboxymethyl starch. A comparative dissolution study was conducted using the USP procedure. Significant differences (p = 0.05) were found among the formulations relative to in vitro dissolution rates over a two-hour sampling period. The formulations prepared with lactose consistently ranked near the top (Newman-Keuls multiple range test) while the formulation prepared with sodium carboxymethyl starch ranked last at each sampling time except 3 min.

Semiautomated System for High-Pressure Liquid Chromatographic Determination of Dissolution Rate of Fludrocortisone Acetate Tablets

A new semiautomated high-pressure liquid chromatographic (HPLC) system is described to determine the dissolution rate of fludrocortisone acetate tablets. The system uses a miniaturized dissolution basket and shaft assembly having the same geometry as that given in USP XIX. This reduced size permits use of smaller volumes of dissolution medium, allowing most very low dose oral solid dosage forms to be handled. The USP dissolution kettle was also replaced with a new miniaturized vessel that continuously filters the sample solution before it enters the flow system. Volumes of dissolution medium as small as 15ml can be accommodated, depending on the sensitivity of the assay employed and the solubility of the drug substance under study. The concentration of fludrocortisone acetate in solution was monitored by a new HPLC system employing a reversed-phase column compatible with the aqueous dissolution medium used. A comparative dissolution study of different lots was made using different basket rotation speeds.