• Archives of Pharmacal Research
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• v.18 no.1
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• pp.22-26
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• 1995

The solubility and dissolution rate of naproxen (NPX) complexed with 2-hydroxypropyl-.betha.-cyc-lodextrin (2-HP.betha.CD) using coprecipitation, evaporation, freeze-drying and kneading method were investigated. Solubility of NPX linearly increased (correlation cefficient, 0.995) as $2-HP\betaCD$ concentraction increased, resutling in $A_l$ type phase solubility curve. Inclusion complexes prepared by four different methods were compared by different methods were compared by dfferential scanning calorimetry(DSC). The NPX showed sharp endothemic peak around $156^{\circ}C$ but inclusion complexes by evaporation, freeze-drying and kneading method showed very broad peak without distinct phase transtion temperature. In contrast, inclusion complex prepared by coprecipitation method resulted in detectable peak around $156^{\circ}C$ which is similar to NPX, suggesting incoplete formation of indusion co plex. Dissolution rate of inclusion complexes prepared by evaporation, frezz-drying and kneding except coprecipitation method was largely enhanced in the simultaed gastric and intestinal fluid when compared to NPX powder and commercial $NA-XEN^\registered$tablet. However, about 65% of NPX in gstric fluid. in case of inclusion complex prepared by coprecipitation method, formation of inclusion complex appeared to be incoplete, resulting in no marked enhancement of dissolution rate. From these findings, inclusion complexes of poorly water-soluble NPX with $2-HP\betaCD$ were useful to increase soubility and dissolution rate, resting in enhancement of bioavailability and minimization of gastrointestinal toxicity of drug upon oral administration of inclusion complex.

• Journal of Pharmaceutical Investigation
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• v.25 no.1
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• pp.31-36
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• 1995

Solid dispersions and inclusion complex were prepared for the enhancement of solubility and dissolution rate of poorly water-soluble ibuprofen(IPF) as a model drug. Polyethylene glycol 4000(PEG4000) and polyvinylpyrrolidone(PVP) were used for the preparation of solid dispersion. $2-Hydroxypropyl-{\beta}-cyclodextrin(2-HP{\beta}CD)$ was also used for the preparation of inclusion complex. The solubility of IPF increased as the concentration of PEG4000, PVP and $2-HP{\beta}CD$ increased. Solubilization capacity of $2-HP{\beta}CD$ was increased about 10 times when compared to PEG 4000 and PVP. The dissolution rate of drug from solid dispersions and inclusion complex in the simulated gastric fluid was enhanced when compared to pure IPF and commercial $BR4^{\circledR}$ tablet as a result of improvement of solubility. In case of solid dispersions, dissolution rate of drug was proportional to polymer concentration in the formulation. The marked enhancement of dissolution rate of drug by inclusion complexation with $2-HP{\beta}CD$ was noted. However, dissolution rate of drug from solid dispersions and inclusion complex in the simulated intestinal fluid was not significant because IPF was readily soluble in that condition. From these findings, water-soluble polymers and cyclodextrin were useful to improve solubility and dissolution rate of poorly water-soluble drugs. However, easiness and reliability of preparation method, scale-up and cost of raw materials must be considered for the practical application of solid dispersion and inclusion complex in pharmaceutical industry.

• Journal of Pharmaceutical Investigation
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• v.6 no.3
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• pp.48-57
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• 1976

An enhancement in the dissolution rate of the drug should facilitate its GI absorption if the absorption process is dissolution rate limited. One of the need for the techniques that can potentially enhance the dissolution rate and extent of absorption of hydrophobic drugs is the formation of coprecipitates with pharmacologically inert, polymeric materials. The physicochemical modification offers the advantage of possibly enabling one to administer the drug orally in a form from which it is most available for GI absorption. Several $investigation^{1-15)}$ demonstrated that the formation of solid dispersions or coprecipitates of relatively water-insoluble drugs with various pharmacologically inert carriers can increase singnificantly their in vitro dissolution rates. However, little information is available in the literature related to the dissolution rate patterns of furosemide, a water-insoluble diurectices, with respect to the sort of copolymer and the ratio of coprecipitates as a function of time, respectively. The purpose of the present investigation was to ascertain, the general applicability of the copolymers to use fore more fast, enhanced dissolution techniques of furosemide. To accomplish the need for enhancement in the dissolution rate of furosemide, varying ratio coprecipitates with different water-soluble polymers, such as polyvinylpyrrolidone (PVP), polyethylene glycol 4000(PEG 4000), and polyethylene glycol 6000 (PEG 6000), were quantitatively studied by comparing their dissolution characteristics of furosemide. The dissolution patterns of pure furosemide, varying ratio furosemide-PVP coprecipitates, (1:2, 1:5, and 1:9(w/w)), furosemide-PEG 4000 coprecipitates (1:4, 1:9, and 1:19(w/w), furosemide-PEG 6000 coprecipitates(1:4, 1:9, and 1:19(w/w)), and the same ratio physical mixtures, respectively, were compared by the amount dissolved as a function of time.

• Journal of Korean Vacuum Science & Technology
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• v.4 no.4
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• pp.102-106
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• 2000

We report scanning force microscope (SFM) observations of enhanced calcite dissolution in aqueous solution due to mechanical stimulation induced by the SFM tip. Images and mechanical treatment were performed in saturated ($\geq$ 60 ${\mu}{\textrm}{m}$) CaCO$_3$ solution adjusted to pH~9. Small area scans of monolayer steps significantly increased the step velocity in the scanned area (in the direction corresponding to dissolution) when the applied contact force is above about 160 nN fer the tips employed. The step velocity could be increased at least an order of magnitude by scanning at even higher contact forces (e.g.,270nN). This enhancement is a function of step orientation relative to the calcite lattice. Indentations near preexisting steps also locally enhance the step velocity. We present evidence that the higher dissolution rates are caused by stress-induced increases in the rate of double-kink nucleation.

• Journal of Pharmaceutical Investigation
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• v.17 no.4
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• pp.175-181
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• 1987

To increase the dissolution rate of furosemide, chitin and chitosan which are widely occurring biodegradable natural materials were used as drug carriers. The ground mixtures of furosemide with chitin or chitosan were prepared by grinding in a ball mill. The ground mixture showed a faster and more enhanced dissolution rate than the physical mixture or intact furosemide. The crystalline peaks of furosemide disappeared in the ground mixtures indicating the production of amorphous form. The comparison of infrared spectra of the physical mixture and the ground mixture showed an interaction such as association between the functional groups of furosemide and chitin or chitosan in the molecular level. The weight losses in TGA curves showed all the same patterns. However, the endothermic peak due to the fusion of furosemide in DTA curve disappeared in the ground mixture indicating the different thermal property. The dissolution of furosemide from ground mixtures was fast in the order of chitosan and then chitin. The co-grinding technique with chitin or chitosan provided a promising way enhancing the dissolution rate of practically insoluble drug.

• Journal of Pharmaceutical Investigation
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• v.13 no.3
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• pp.100-103
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• 1983

Coprecipitates of sulpiride and polyethylene glycol (PEG) decrease the dissolution rate of sulpiride and the degree of decrease is reversely proportional to molecular size of PEG and proportional to increase of PEG ratios in coprecipitates. The physical mixtures of sulpiride and PEG increase the dissolution rate of sulpiride.

• Journal of Pharmaceutical Investigation
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• v.20 no.4
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• pp.193-198
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• 1990

To increase the dissolution rate of furosemide, cogrinding or coprecipitating of furosemide with povidone was carried out. The ground mixture of furosemide with povidone was prepared by cogrinding in a ceramic ball mill and the coprecipitate was prepared by solvent method using methanol. The povidone ground mixture and the coprecipitate showed a faster and more enhanced dissolution rate than the physical mixture or intact furosemide. The IR, DTA and TGA studies showed the physicochemical modifications of furosemide from the ground mixture and the coprecipitate. An interaction, in the ground mixture and in the coprecipitate, such as association between the functional groups of furosemide and povidone might occur in the molecular level. The coprecipitating and cogrinding techniques with povidone provided a promising way to increase the dissolution rate of poorly soluble drugs.

• Journal of Pharmaceutical Investigation
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• v.18 no.2
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• pp.43-47
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• 1988

In order to increase the dissolution characteristics of relatively water-insoluble metoclopramide (MCP), coprecipitates of MCP with polyvinylpyrrolidone (PVP), polyethylene glycol (PEG) 1000, 4000 or 6000 were prepared in various drug to polymer ratios. The dissolution rate of MCP-PVP coprecipitate was greater than those of MCP alone, MCP-PVP physical mixture and MCP-PEG coprecipitates. The dissolution rate of MCP-PEG 6000 coprecipitate was greater than those of MCP-PEG 1000 and MCP-PEG 4000 coprecipitates. The dissolution half-lives $(T_{50%})$ for MCP alone and 1:5 (w/w) MCP-PEG 6000 coprecipitate were determined by the log-probit method at $37^{\circ}C$ and found to be 4.17 and 0.98 min, respectively.

• Journal of Pharmaceutical Investigation
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• v.16 no.1
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• pp.36-41
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• 1986

The ground mixtures of ketoprofen with chitin or chitosan were prepared by grinding in a ball mill to increase the dissolution rate. The ground mixture showed a faster and more enhanced dissolution rate than the physical mixture or intact ketoprofen. The X-ray diffraction peaks indicated the production of the amorphous form of ketoprofen in the ground mixture. An interaction, in the ground mixture, such as association between the functional groups of ketoprofen and chitin or chitosan might occur in the molecular level. The endothermic peak due to the fusion of ketoprofen disappeared in the ground mixture indicating the different thermal property. The co-grinding technique with chitin or chitosan provided a promising way enhancing the dissolution rate of practically insoluble drug.

• Journal of Pharmaceutical Investigation
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• v.18 no.4
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• pp.181-186
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• 1988

Inclusion complex of sulfamethoxazole with ${\beta}-cyclodextrin$ was prepared by freeze-drying method in molar ratios of 1:1, 1:1.25, 1:1.5 and 1:1.75, and the complex formation was identified by ultraviolet and infrared spectroscopies, powder X-ray diffractometry and differential scanning calorimetry. Dissolution rate and solid state stability of the complex were investigated in comparison with those of sulfamethoxazole powder and the physical mixture of sulfamethoxazole with ${\beta}-cyclodextrin$. As a result, the dissolution rate and the stability of solid complexes in various relative humidity conditions increased more remarkably than those of sulfamethoxazole powder and physical mixture. But the difference according to molar ratio of the complex was not recognized.