• Journal of Pharmaceutical Investigation
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• 제26권3호
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• pp.187-192
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• 1996

The matrix tablet containing sodium alginate and $CaHPO_4$ can release drugs in a controlled fashion from hydrogel with gelling and swelling due to their interaction as water penetrates the matrices of the tablet. The purpose of this study was to evaluate release characteristics of the matrix tablet varying the amount of sodium alginate, $CaHPO_4$ and other excipients such as chitosan, hydroxypropyl methylcellulose (HPMC) and $Eudragit^{\circledR}$ RS100 in the simulated gastric and intestinal fluid. The practically soluble ibuprofen was used as a model drug. The release profiles of matrix tablet in the gastric fluid as a function of sodium alginate/$CaHPO_4$ ratio was not pronounced because of low solubility of drug and stability of alginate matrices. However, release rate of drug from the matrix tablet in the intestinal fluid was largely changed when sodium alginate/$CaHPO_4$ ratio was increased, suggesting that the ratio of sodium alginate/$CaHPO_4$ was an important factor to control the gelling and swelling of the matrix tablet. The incorporation of other excipients into the matrix tablet also influenced the release rate of drug. The chitosan and HPMC decreased the release rate of drug. No release of drug was occurred when $Eudragit^{\circledR}$ RS100 was added into the tablet. The retarded release of matrix tablet when excipients were added resulted from the hindrance of swelling and gelling of the matrix tablet containing sodium alginate and $CaHPO_4$. The hardness and bulk density of the matrix tablet was not correlated with release rate of drug in the study. From these findings, the ratio of sodium alginate and $CaHPO_4$ in the matrix tablet in addition to incorporation of excipients could be very important to control the release rate of drug in dosage form design.

• Archives of Pharmacal Research
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• 제28권5호
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• pp.604-611
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• 2005

Polyethylene glycol (PEG) 6000-based solid dispersions (SDs), by incorporating various pharmaceutical excipients or microemulsion systems, were prepared using a fusion method, t o compare the dissolution rates and bioavailabilities in rats. The amorphous structure of the drug in SDs was also characterized by powder X-ray diffractometry (XRD) and differential scanning calorimetry (DSC). The ketoconazole (KT), as an antifungal agent, was selected as a model drug. The dissolution rate of KT increased when solubilizing excipients were incorporated into the PEG-based SDs. When hydrophilic and lipophilic excipients were combined and incorporated into PEG-based SDs, a remarkable enhancement of the dissolution rate was observed. The PEG-based SDs, incorporating a self microemulsifying drug delivery system (SMEDDS) or microemulsion (ME), were also useful at improving the dissolution rate by forming a microemulsion or dispersible particles within the aqueous medium. However, due to the limited solubilization capacity, these PEG-based SDs showed dissolution rates, below 50% in this study, under sink conditions. The PEG-based SD, with no pharmaceutical excipients incorporated, increased the maximum plasma concentration (C$_{max}$) and area under the plasma concentration curve (AUC$_{0-6h}$) two-fold compared to the drug only. The bioavailability was more pronounced in the cases of solubilizing and microemulsifying PEG-based SDs. The thermograms of the PEG-based SDs showed the characteristic peak of the carrier matrix around 60$^{\circ}C$, without a drug peak, indicating that the drug had changed into an amorphous structure. The diffraction pattern of the pure drug showed the drug to be highly crystalline in nature, as indicated by numerous distinctive peaks. The lack of the numerous distinctive peaks of the drug in the PEG-based SDs demonstrated that a high concentration of the drug molecules was dissolved in the solid-state carrier matrix of the amorphous structure. The utilization of oils, fatty acid and surfactant, or their mixtures, in PEG-based SD could be a useful tool to enhance the dissolution and bioavailability of poorly water-soluble drugs by forming solubilizing and microemulsifying systems when exposed to gastrointestinal fluid.

• Advances in Traditional Medicine
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• 제5권1호
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• pp.29-36
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• 2005

Polysaccharide hydrogels constitute a structurally diverse class of biological macromolecules with a wide range of physicochemical properties. They also constitute important members of the family of industrial water-soluble polymers. They find application in Pharmacy as binders, disintegrants, suspending, emulsifying and sustaining agents. According to the International Pharmaceutical Excipients Council (IPEC), an excipient must have an established safety profile. Hence, in the present study, in vitro cytotoxicity on Vero and HEp-2 cell lines, and in vivo acute toxicity in rats were carried out to establish the safety of polysaccharide hydrogels from the seeds of Plantago ovata and Ocimum basilicum. The in vitro cytotoxicity was determined by MTT and SRB assays. In the in vivo acute toxicity, the effects of three different doses of hydrogels (100, 200 and 400 mg/kg body weight) on food and water intake, body weight, biochemical and hematological parameters were studied. The results of in vitro did not show any cytotoxicity on both the cell lines used. In the in vivo acute toxicity, the hydrogels did not show any toxic symptoms in all three dose levels. This establishes the safety of the selected hydrogels. Hence, they can be used as excipients in pharmaceutical dosage forms.

• 대한약침학회지
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• 제25권4호
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• pp.317-325
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• 2022

Polymers are the major constructive material of pharmaceutical formulations that play a prime role in designing effective drug-delivery systems and releasing drugs at their sites of application. Polymers are composed of multiple repeating units of high molecular mass components with attendant properties. Most synthetic polymers are non-biocompatible, expensive, and extremely inclined to deliver adverse impacts. Meanwhile, edible polymers obtained from natural sources have gained remarkable recognition for their promising use in modern medicine. Moreover, polymers derived from natural sources are generally preferred due to certain of their unique features such as abundant availability, biocompatibility, nontoxicity, economical, safe, and effective functions that fit the purpose. Polysaccharides including starch, cellulose, hemicellulose, pectin, and mucilage are identified as a major class of naturally obtained molecules that have a substantial role as functional polymers. This review summarizes the potential role of polysaccharides derived from vegetable sources such as adhesives, anticaking agents, binders, disintegrants, emulsifiers, film-framing agents, and thickeners. This is simply an opportunity to abandon synthetic excipients that hurt our bodies and think back to nature from where we originate.

• Archives of Pharmacal Research
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• 제26권4호
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• pp.330-337
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• 2003

The effect of sixteen excipients on the transport of recombinant human epidermal growth factor (rhEGF) across Caco-2 cell monolayers was examined at $37^{\circ}C$. The apparent apical to basolateral (A-B) permeability ($P_{app}$) of 30 $\mu$ M rhEGF was $8.15\times 10^{-7}$ cm/sec, indicative of a poor level of absorption in the GI tract. The Papp was 1.7- and 6.3-fold greater than the $P_{app}$ in the basolateral to apical (B-A) direction and the A-B permeability of mannitol, respectively, and decreased dramatically to a negligible level at $4^{\circ}C$, consistent with a receptor mediated transcytosis of rhEGF. The stability of rhEGF was very poor, undergoing more than 85% degradation in 2 h in the transport medium at $37^{\circ}C$. A significant increase in the $P_{app}$ could be achieved by the addition of certain excipients, as exemplified by 23, 21, 20 and 16-fold increases, in the presence of sodium taurochenodeoxycholate (NaTCDC), sodium taurodeoxycholate (NaTDC), sodium glycodeoxycholate (NaGDC) and sodium laurylsulfate (SLS) (all at a concentration of 1 % w/v), respectively. A significant increase in stability could also be achieved by the addition of some of the excipients, as represented by 1 % SLS, which nearly completely stabilized the rhEGF. Unfortunately, however, an increase in the $P_{app}$ of rhEGF could not be achieved without a simultaneous and extensive decrease in the integrity of the cell membranes. Thus, more efficient excipients, that specifically enhance the permeation of rhEGF and do not alter the membrane integrity, should be pursued in order to safely enhance the permeation of rhEGF.

• Journal of Pharmaceutical Investigation
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• 제5권2호
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• pp.57-62
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• 1975

It was many differances to evaluate of the effect of excipients on colour fading in FD & C Yellow No.5 by use Tintometer and nearly is not effective in FD & C Red No. 2. When we observed colour fading in suger coating formulations by tintometer, FD & C Red No.2 was appeared to follow zero order reaction and FD & C Yellow No. 5 was not follow zero order reaction or first order reaction. Also, we could know the tendency of colour fading by visible spectrum, but it was net suitable method for this experiment more than by tintometer. The relative colour fading effect of the surfactants(Polysorbate) was as follows: Tween 60> Tween 80> Tween 20. In addition to, Benzalkonium chloride was reacted with FD & C Yellow No.5, so the stronger colour was appeared. On the other hand, the weaker colour was appeared in FD & C Red No.2. While, the sunscreening agents was not almost effective in colour fading of FD & Yellow No. 5 and FD & C Red No. 2.

• Archives of Pharmacal Research
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• 제26권12호
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• pp.1002-1008
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• 2003

Ferulic acid (3-methoxy, 4-hydroxy cinnamic acid) is a flavoid component possessing antioxidant property. The compound is currently under development as a new drug candidate for the treatment of the dementia. The objective of this preformulation study was to determine the physicochemical properties of ferulic acid. The n-octanol to water partition coefficients of ferulic acid were 0.375 and 0.489 at the pHs of 3 and 10, respectively. Accelerated stability study for ferulic acid indicated that the t 90 value for the drug was estimated to be 459 days at $25^{\circ}C$. Ferulic acid was also found to be unstable under the relative humidity of more than 76%, probably because of the hygroscopic nature of the drug. In order to study compatibility of ferulic acid with typical excipients, potential change in differential scanning calorimetry spectrum was studied in 1: 1 binary mixtures of ferulic acid and typical pharmaceutical excipients (e.g., Aerosil, Avicel, CMC, Eudragit, lactose, PEG, PVP, starch and talc). Avicel, CMC, PVP and starch were found to be incompatible with ferulic acid, indicating the addition of these excipients may complicate the manufacturing of the formulation for the drug. Particle size distribution of ferulic acid powder was in the size range of 10-190 $\mu$m with the mean particle size of 61 $\mu$m. The flowability of ferulic acid was apparently inadequate, indicating the granulation may be necessary for the processing of the drug to solid dosage forms. Two polymorphic forms were obtained by recrystallization from various solvents used in formulation. New polymorphic form of ferulic acid, Form II, was obtained by recrystallization from 1,4-dioxane. The equilibrium solubility for Form I was approximately twice of that for Form II. The dissolution rate of Form II was higher than that of Form I in the early phase (<6 min). Therefore, these physicochemical information has to be taken in the consideration for the formulation of ferulic acid.

• Journal of Pharmaceutical Investigation
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• 제32권4호
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• pp.305-311
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• 2002

In order to evaluate the effect of poloxamer 407 content on the dissolution profiles of pellets, diltiazem HCl (DTL) core pellets were prepared with poloxamer 407 (50-90% w/w, with lactose as filler) using an extruder and a spheronizer. Any possible interaction between the drug and excipients was evaluated using DSC, IR and TLC. Dissolution tests were performed using USP basket method. In addition, scanning electron micrograph was performed to examine the surface roughness and cross sections. The release of DTL from the core pellets was decreased with increasing poloxamer 407 content. Cracks appeared on the surface of the core pellets with increasing the poloxamer 407 content, which may play a role on the retardation of the release of DTL from core pellets. There was no any significant interaction between the drug and excipients employed to prepare the core pellets.

• Bulletin of the Korean Chemical Society
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• 제35권8호
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• pp.2577-2580
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• 2014

• Journal of Pharmaceutical Investigation
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• 제15권2호
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• pp.45-52
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• 1985

For the model tablets using mannitol and Avicel PH 101 as excipients, the patterns of disintegration and dissolution from the differences of physical properties were investigated. It was found that the patterns in the dissolution and binding forces in the interaction of materials by estimates of solid-solid or liquid surface free energy due to cohesive or adhesive properties of materials, and solid surface free energy in binding forces of tablet should be considered as an important factor in dissolution processes.