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1.
AbstractThe influence of three different tableting diluents and three different forms of ascorbic acid on the color change of vitamin C have been investigated. Ten different direct compression formulations were made and subjected to accelerated stability study. Color changes in tablets were monitored with a Tristimulus Colorimeter. It has been found that lactose and Emdex influenced the color change of direct compression ascorbic acid tablets to a lesser degree than Sorbitol. Further, Calcium Ascorbate brought changes in the color of the tablets at a faster rate than C-90 or Sodium Ascorbate. A good correlation of 0.998 was found for a linear relation of visual color rating against normalized total color difference values of these tablets. 相似文献
2.
AbstractContext: To ensure safe oral administration, pediatric patients require an appropriate dosage form to be swallowed without relevant difficulties. Ex tempore hydrated powders, forming viscous pulp “on a spoon”, have recently gained much interest as pediatric formulations. The aim of this study was to evaluate the viscosity-increasing substances and disintegrants, alone or in mixtures, as excipients suitable for preparing such formulations, with candesartan and valsartan chosen as model active substances. Methods: The mixtures of excipients were prepared in the form of powders, granules or lyophilizates, which were evaluated in terms of their ability to form a homogenous mass after hydration with a small amount of water. The best compositions were tested with candesartan cilexetil and valsartan (2% and 10% w/w, respectively). Performed studies include macroscopic, organoleptic and microscopic observations, as well as a textural analysis, determination of gelation time and rheological measurements. Results: Mixtures of guar gum, lactose and one of the disintegrants (F-Melt M, Prosolv 50, Prosolv Easy, Lycatab, Pharmaburst, Pearlitol) demonstrated the best properties. With regard to drug-incorporating formulations, granules were evaluated as the most satisfying form, while the functional properties of lyophilized formulations were poor. Conclusion: Granules with candesartan cilexetil (2%) were found to be the most promising for further development. 相似文献
3.
Context: Enhancement of aqueous solubility of very slightly soluble Miconazole Nitrate (MN) is required to widen its application from topical formulation to oral/mucoadhesive formulations. Objective: Aim of the present investigation was to enhance the aqueous solubility of MN using binary and ternary mixture approach. Materials and methods: Binary mixtures such as solvent deposition, inclusion complexation and solid dispersion were adopted to enhance solubility using different polymers like lactose, beta-cyclodextrin (β-CD) and polyethylene-glycol 6000 (PEG 6000), respectively. Batches of binary mixtures with highest solubility enhancement potentials were further mixed to form ternary mixture by a simple kneading method. Drug polymer interaction and mixture morphology was studied using the Fourier transform infrared spectroscopy and the scanning electron microscopy, respectively along with their saturation solubility studies and drug release. Results: An excellent solubility enhancement, i.e. up to 72 folds and 316 folds of MN was seen by binary and ternary mixture, respectively. Up to 99.5% drug was released in 2?h from the mixtures of MN and polymers. Discussion: Results revealed that solubility enhancement by binary mixtures is achieved due to surface modification and by increasing wettability of MN. Tremendous increase in solubility of MN by ternary mixture could possibly be due to blending of water soluble polymers, i.e. lactose and PEG 6000 with β-CD which was found to enhance the solubilizing nature of β-CD. Conclusion: Owing to the excellent solubility enhancement potential of ternary mixtures in enhancing MN solubility from 110.4?μg/ml to 57?640.0?μg/ml, ternary mixture approach could prove to be promising in the development of oral/mucoadhesive formulations. 相似文献
4.
AbstractDSC screening for drug-excipient interactions of a polypharmaceutical capsule dosage form containing salicylamide, ascorbic acid, pyrilamine maleate, phenylephrine hydrochloride, lactose, colloidal silicon dioxide and sodium starch glycolate was performed. 相似文献
5.
Context: Electrostatic forces have been claimed to be a mechanism for aerosol deposition in the lungs. However, the extent of its influence on aerosol performance is not clear, particularly for carrier-drug formulations. Objectives: To prepare lactose-salbutamol powder blends, varying in blend ratio, and identify any relationships between salbutamol dose, electrostatic characteristics and in vitro aerosol performance. Methods: Decanted lactose and micronized salbutamol sulfate was mixed to produce five blends (equivalent to 50, 100, 200, 300 and 400 µg salbutamol per 33?mg of powder). 33?±?1?mg of a blend was loaded into a Cyclohaler? and dispersed into the electrical Next Generation Impactor (eNGI) at an air flow rate of 60?L/min. This was conducted in triplicate for all five lactose-salbutamol blends. Results: Fine particle fraction increased with salbutamol dose, from 5.89?±?1.42 to 21.35?±?2.91%. Specific charge (charge divided by mass) distributions for each blend were greatest in magnitude for the 50 µg blend and similar in magnitude between all other blends. However, in eNGI Stage 1 (>8.06?µm), specific charge decreased from 100 µg (?170.4?±?45.8 pC/µg) to 400 µg (?10.0?±?9.1 pC/µg). Conclusions: The improvement in fine particle fraction with increased salbutamol dose was indicative of fine drug binding to high and low energy sites on the lactose carrier surface. This finding was supported by electrostatic charge results, but the aerosol charge itself was not found to influence aerosol performance by electrostatic forces. 相似文献
6.
AbstractTablets which were prepared from separate formulations of Emcompress Standard R, a commercially available directly compressible granulation, with ascorbic acid, folic acid, and thiamine hydrochloride were subjected to accelerated aging conditions and studied for chemical stability and such physical parameters as hardness, friability, and disintegration time. Other physical factors which could affect the interpretation of the data, such as moisture content, particle size distribution, angle of repose, weight variation, and hardness were also studied using fresh samples.Accelerated aging showed that the ascorbic acid formulation was chemically unstable; the tablets became soft, the frability increased markedly, and the disintegration time decreased. The folic acid formulation was chemically stable, but the tablets became soft, the friability increased, and disintegration time increased. The thiamine hydrochloride formulation was also chemically stable—the tablets became soft, the disintegration time decreased, and the friability increased. 相似文献
7.
AbstractSpray-dried rice starch (SDRS), microcrystalline cellulose (MCC), lactose (L), pregelatinized starch (PS), and dibasic calcium phosphate (DCP) were studied for their flow behaviors and tableting properties. Both flow rate and percent compressibility values indicated that SDRS exhibited excellent flowability. The increase in magnesium stearate content reduced the hardness of MCC and SDRS tablets; however, general tablet properties were still acceptable while the PS tablets were unsatisfactory at high lubricant concentrations. The hardness of L or DCP tablets was not affected by the lubricant. The disintegration of L tablets was prolonged with the increased lubricant concentration while that of PS tablets seemed to be decreased due to softened tablets. The disintegration times of MCC and SDRS tablets seemed to be independent of the lubricant added. With respect to the dissolution, SDRS-based tablets offered fast and complete release of the drug regardless of its solubility. SDRS, L, and DCP exhibited comparable carrying capacity for ascorbic acid. The best dilution potential was obtained with MCC while the worst was obtained with PS. 相似文献
8.
AbstractSeveral sustained-release tablet formulations with acceptable pharmacokinetic properties were found to be unstable because of the effects of lactose. Because the pharmacokinetic properties were acceptable, an attempt was made at developing stable formulations that reproduced the in vitro drug release characteristics of the unstable formulations. Through the use of a statistically designed mixture experiment, alternative formulations were generated and tested for dissolution. The dissolution data collected in the mixture experiment were used to develop a statistical regression model for identifying formulations with dissolution rates equal to those of the unstable formulations. The form of the regression model was based on the Higuchi equation. The data analysis indicated that it is possible to generate dissolution profiles that reproduce those of the original formulations by adjusting the ratios of Methocel® K4MCR Premium and Methocel KWOMCR Premium and by replacing the detrimental lactose with calcium phosphate dibasic anhydrous. 相似文献
9.
Objective: The suitability of the rabbit as an animal model for the primary screening and selection of the pilot scale batches during the early stages of the formulation development was studied. Materials and methods: Three modified-release formulations of aminophylline consisted of Carbopol® 971P/HPMC K4M (F-I), and HPMC K100M (F-II) or HPMC K4M (F-III) were used. Commercial products were Aminofilin retard 350?mg tablets, Srbolek, Serbia (R-I) and Phyllocontin ® 350, tablets Purdue Frederic, Canada (R-II). Results: Calculated release rate constants and the ?2 values between R-I/F-I (84.1) and R-II/F-III (83.4) indicated similar in vitro release while the coefficient n showed presence of different mechanisms of release from Anomalous transport, Fickian diffusion to Case-II transport. Higher Tmax, was found in the rabbits, dosed with F-II (12.00?h), F-III (10.50?h), and R-II (15.00?h) formulation. The highest Cmax (9.22?mg/L) was obtained with F-II, similar lower values was seen for F-I and F-III, while commercial products showed the lowest values R-I (5.58?mg/L) and R-II (4.18?mg/L). Higher AUC values were detected for all three formulations (from 115.90 to 204.06 mgh/L) in relation to commercial products (105.33 and 113.25 mgh/L). Discussion and conclusion: The results demonstrated a good correlation of Level A ( r2 = 0.97) for the two formulations (F-I, F-III) and commercial product (R-I) indicates that there is a reasonable assumption that the rabbit might be use as a model for the preliminary comparison of scale up formulations in the early stages of the product development. 相似文献
10.
Objective: The present investigation was aimed at optimizing of estradiol (E2) loaded l-amino acid derivatives organogel formulations resulting in improved the high initial release problems and sustained release of E2. Methods: The visco-elastic properties of blank organogels were measured by rheometer. The E2 organogel formulations were optimized using a central composite design. Also, the effect of gelator structure and composition of the gel formulations on release behavior ( in vitro and in vivo) had been studied. Results: The change of the gelator structure could affect significantly the stiffness of the implants. The release behavior of gel without N-Methyl-2-pyrrolidinone (NMP) was controlled by gel corrosion only. While the drug release of the gel with NMP was controlled by both corrosion and diffusion. The high initial release problems of the organogels were improved by optimizing the formulations. The system consisting by N-Lauroyl l-lysine methyl ester (LLM) derivative in the oil indicated the lowest initial drug release, showed a much lower blood drug level and maintained a steady state for nearly 1 month. Conclusion: Organogels based on l-lysine methyl ester derivative were ideal carriers for long-term parenteral administration of E2. 相似文献
11.
The influence of three different tableting diluents and three different forms of ascorbic acid on the color change of vitamin C have been investigated. Ten different direct compression formulations were made and subjected to accelerated stability study. Color changes in tablets were monitored with a Tristimulus Colorimeter. It has been found that lactose and Emdex influenced the color change of direct compression ascorbic acid tablets to a lesser degree than Sorbitol. Further, Calcium Ascorbate brought changes in the color of the tablets at a faster rate than C-90 or Sodium Ascorbate. A good correlation of 0.998 was found for a linear relation of visual color rating against normalized total color difference values of these tablets. 相似文献
12.
AbstractSeveral crystal structures of Sorbitol may be encountered. Eleven Sorbitol samples from five different manufacturers were studied by X Ray diffraction and differential scanning calorimetry. Three crystalline forms were identified. The γ form is the most stable. One of these samples was constituted by the pure γ form.Sorbitol is usually considered as a very hygroscopic excipient. We studied this most stable Sorbitol for its technological and biopharmaceutical properties in tablet formulation.Aspirin and Acid Ascorbic tablets were prepared with γ Sorbitol as a diluent, in high concentration, by direct compression. Three disintegrants were tested: maize starch, Kollidon CL R, Ac Di Sol R. Using either lactose or γ Sorbitol as a diluent, different batches of tablets were prepared with the same proportion of diluent and in the same conditions.Compression properties, hardness, disintegration time, dissolution rate and stability in moist conditions were studied.The tablets containing γ Sorbitol show:- a better ratio compression force/hardness- a longer time of disintegration and dissolution- the very great importance of the choice of the disintegrant: Ac Di Sol was much better than Kollidon CL or Maïze starch in this case of formulation: conserved during one year at 80% Relative Humidity, tablets with γ Sorbitol and Ac Di Sol kept their aspect and their biopharmaceutical properties very well. A slightly greater acid ascorbic alteration with Sorbitol as a diluent than with lactose can be noticed.It seems that γ Sorbitol is a stable diluent if the Relative Humidity is lower than 80%. Then it should be avoided with drugs too sensitive to moisture like ascorbic acid.In spite of a slower release time, its hardening power and its very good compression properties can be of great interest. 相似文献
13.
Objective: The aim of this work was to develop an amorphous solid dispersions/solutions (ASD) of a poorly soluble drug, budesonide (BUD) with a novel polymer Soluplus ® (BASF, Germany) using a freeze-drying technique, in order to improve dissolution and absorption through the nasal route. Significance: The small volume of fluid present in the nasal cavity limits the absorption of a poorly soluble drug. Budesonide is a corticosteroid, practically insoluble and normally administered as a suspension-based nasal spray. Methods: The formulation was prepared through freeze-drying of polymer-drug solution. The formulation was assessed for its physicochemical (specific surface area, calorimetric analysis and X-ray powder diffraction), release properties and aerodynamic properties as well as transport in vitro using RPMI 2650 nasal cells, in order to elucidate the efficacy of the Soluplus–BUD formulation. Results: The freeze-dried Soluplus–BUD formulation (LYO) showed a porous structure with a specific surface area of 1.4334?±?0.0178 m 2/g. The calorimetric analysis confirmed an interaction between BUD and Soluplus and X-ray powder diffraction the amorphous status of the drug. The freeze-dried formulation (LYO) showed faster release compared to both water-based suspension and dry powder commercial products. Furthermore, a LYO formulation, bulked with calcium carbonate (LYO-Ca), showed suitable aerodynamic characteristics for nasal drug delivery. The permeation across RPMI 2650 nasal cell model was higher compared to a commercial water-based BUD suspension. Conclusions: Soluplus has been shown to be a promising polymer for the formulation of BUD amorphous solid suspension/solution. This opens up opportunities to develop new formulations of poorly soluble drug for nasal delivery. 相似文献
14.
ABSTRACT In this study, the effect of drug loading on the nasal absorption of insulin was determined. Human insulin was loaded into different drug carriers by two methods: supercritical fluid processing and freeze-drying. The powder formulations were characterized and then evaluated after nasal administration to alloxan induced diabetic rabbits at a dose of 5U/kg and 7.5U/kg. The blood glucose levels and serum insulin levels were monitored for five hours after administration of insulin formulations. The drug carriers evaluated were: ammonium glycyrrhizinate (AG), polyacrylic acid (PAA), cross-linked polyacrylic acid (CPAA), polyethylene oxide (PEO) and chitosan (CHTN). Nasal administration of AG infused with insulin by carbon dioxide resulted in absolute bioavailability of 9.81% as compared to 2.86% observed with same powder loaded with insulin by freeze-drying. 8.05% bioavailability was obtained with PAA powder loaded with insulin by carbon dioxide as compared to much lower absorption seen with freeze-dried formulation. Similarly a two fold increase in absolute bioavailability was observed when carbon dioxide infused CPAA powder formulation was compared to the lyophilized powder. Nasal administration of PEO and CHTN loaded with insulin by carbon dioxide resulted in bioavailabilities of 1.55% and 1. 18% respectively. The drug-loading process seems to have a significant effect on nasal absorption of insulin. The powders loaded with insulin by carbon dioxide infusion resulted in significantly higher absorption. The exact mechanism is still not known and a possible explanation for increased absorption may be due to improved stability of insulin in carbon dioxide infused formulations. Among the powders evaluated, polyacrylic acid and ammonium glycyrrhizinate prepared by carbon dioxide infusion as drug-loading method seem to offer good potential for development of nasal powder dosage forms for insulin. 相似文献
15.
AbstractThis study is the second in a series that examines the characterizing and selection of suitable grades of lactose for capsule formulation development. Based upon the previous study, four grades were selected for further study. The effects of drug load and operational variables on formulations derived from these four lactose types were evaluated for physicochemical and mechanical attributes of plugs and their capsules on an instrumented dosing-disc capsule filling machine (H&H KFM/3) using acetaminophen as a model, highly soluble and poorly compressible drug. The results obtained were as follows: (1) flowability reduced upon increasing drug load; (2) powder bed height (PBH) and compression force (CF) had positive significant effect on plug weight ( p?<?0.05); (3) ejection force was positively and significantly correlated with increasing speed and CF ( p?<?0.05); (4) AL capsule plugs had the highest plug crushing force which was followed by DCL15; (5) the crushing strength of plugs made from DCL11 increased with increasing acetaminophen concentration; (6) higher CF had a significant negative impact on acetaminophen release at 15?min time point ( p?<?0.05); (7) at 10% and 40% drug load, formulations containing AL showed the quickest drug release; and (8) increased drug load had a significant negative impact on the release rate at 15 and 45?min time points ( p?<?0.05). Overall, the results from this study provides information on risk based assessment of filler selection based on drug load and the range of machine operating variables which will help in defining criteria for meeting key quality attributes for capsule formulation development. 相似文献
16.
Context: Dry powder inhalers (DPIs) consisting of a powder mixture containing coarse carrier particles (generally lactose) and micronized drug particles are used for lung drug delivery. The effective drug delivery to the lungs depends on size and shape of carrier particles. Thus, various methods have been proposed for engineering lactose particles to enhance drug delivery to lungs. Objective: The objective of current work was to assess suitability of electrospray technology toward crystal engineering of lactose. Further, utility of the prepared lactose particles as a carrier in DPI was evaluated. Materials and methods: Saturated lactose solutions were electrosprayed to obtain electrosprayed lactose (EL) particles. The polymorphic form of EL was determined using Fourier transform infrared spectroscopy, powder X-ray diffractometry, and differential scanning calorimetry. In addition, morphological, surface textural, and flow properties of EL were determined using scanning electron microscopy and Carr’s index, respectively. The aerosolization properties of EL were determined using twin-stage impinger and compared with commercial lactose particles [Respitose® (SV003, Goch, Germany)] used in DPI formulations. Results and discussion: EL was found to contain both isomers (α and β) of lactose having flow properties comparable to Respitose® (SV003). In addition, the aerosolization properties of EL were found to be significantly improved when compared to Respitose® (SV003) which could be attributed to morphological (high elongation ratio) and surface characteristic (smooth surface) alterations induced by electrospray technology. Conclusion: Electrospray technology can serve as an alternative technique for continuous manufacturing of engineered lactose particles which can be used as a carrier in DPI formulations. 相似文献
17.
AbstractMonitoring of the physical state of warfarin sodium (WS) in products is essential for minimizing product quality variability in order to ensure consistent clinical performance. This study reports the development of chemometric models for quantifying the crystalline and amorphous fractions of WS in commercial drug products using NIR spectroscopy. Formulations based on commercially available products with different API to excipient ratio were used for the study. For each content, two formulations containing either lactose monohydrate or lactose anhydrous as the predominant formulation excipient were prepared. Two formulations containing either 100% amorphous WS (AWS) or crystalline WS (CWS) were prepared and mixed in various ratios to obtain sample matrices containing AWS/CWS 0–100%. The uniformity of the samples was confirmed by near infrared chemical imaging. Data were mathematically pretreated by multiplicative signal correction and Savitzky–Golay second derivative. Principal component regression and partial least square regression models were developed from mathematically treated data. All the models showed linear trend for amorphous and crystalline fractions of the WS as indicated by correlation and R2?>?0.99 and >0.98, respectively. The models demonstrated good performance parameters with a low-root mean squared error, standard error and bias. The model predicted CWS and AWS contents were in very close agreement with the actual values. The study indicated the utility of NIR chemometric methods in quantification of the crystalline and/or amorphous fraction of WS in its products. 相似文献
18.
Background: Novel aqueous nano-scaled formulations were developed for hydrophobic oleic acid stabilized monodisperse superparamagnetic magnetite nanocrystals. Methods: In the study, single and mixed lipid amphiphiles based on Cremophor RH-40 (Crem-RH-40), Solutol HS-15 (Sol-HS-15), Phospholipon-100H (PL-100H) and sucrose ester M-1695 (SE-M-1695) were employed at varying concentrations. Isotonicity and physiological pH adjustments were achieved by using 5% w/v mannitol in 10 mM pH 7.4 phosphate buffer. Mannitol also served as lyoprotectant for the freeze drying of selected formulation. The developed formulations were characterized by photon correlation spectroscopy (PCS) and asymmetric flow field flow fractionation methods for their size and size distributions and morphologies were examined by transmission electron microscopy (TEM). Moreover, the potential magnetic resonance imaging (MRI) contrast agent application of a selected formulation was investigated by 1H-NMR relaxometric measurements. Results: The results showed that stable formulations of the nanocrystals with hydrodynamic diameters generally below 100 nm were obtained. Among the developed formulations, the one prepared with 0.75% Crem-RH-40, 0.5% PL-100H and 0.25% SE-M-1695 had a mean hydrodynamic diameter of ~64 nm and zeta potential of ?20 mV. This formulation exhibited low degree of aggregation, high level of incorporation of magnetite nanocrystals and very good stability profile over a period of 6 months. In addition, it showed transverse and longitudinal relaxivities of 221.8 and 32.1 s ?1·mM ?1, respectively with r2/ r1 ratio of 6.9. Conclusion: This study revealed that mixed lipid-based amphiphiles allow stable aqueous formulations of the normally challenging hydrophobic magnetite nanocrystals with potential in vivo MRI contrast applications. 相似文献
19.
Background: (+)-catechin, as the most common catechin isomer, is recognized to be an antioxidant which benefits the skin in many ways. The purpose of the present study was to prepare and evaluate a suitable liposomal delivery systems for (+)-catechin topical application.Methods: In this study, catechin-loaded conventional liposomal delivery system, deformable conventional liposomal delivery system and deformable liposomes prepared by reverse-phase evaporation (REV) method were compared. The three systems were characterized for liposome particle size, zeta-potential, entrapment efficiency, drug release, permeability across porcine skin and catechin deposition in the skin.Results: It was revealed that the size of deformable conventional liposomes before freeze-drying and deformable REV liposomes after freeze-drying range from 335.6?±?71.7?nm to 551.1?±?53.4?nm, respectively, which were considered to be suitable for skin delivery. The deformable REV liposomes had a higher aqueous volume and thus were able to entrap greater amounts of hydrophilic (+)-catechin (50.0?±?5.9%) compared to conventional (30.0?±?3.8%) and deformable conventional liposomes (36.1?±?4.6%). All liposomal formulations exhibited a prolonged catechin release. Compared to deformable liposomes, the REV deformable liposomes showed a significantly better deposition of (+)-catechin while catechin solution did not permeate into the porcine ear skin.Conclusion: Among all formulations studied, deformable REV liposomes were considered to be favorable for catechin topical delivery. 相似文献
20.
Context and objectives: The buccal mucosa presents a unique surface for non-invasive drug delivery and also avoids first-pass metabolism. The objective of this study was the formulation development of polymeric mucoadhesive lyophilized wafers as a matrix for potential buccal drug delivery. Materials and methods: Differential scanning calorimetry (DSC) was used to develop an optimum freeze-cycle, incorporating an annealing step. The wafers were prepared by lyophilization of gels containing three polymers, κ-carrageenan (CAR 911), poloxamer (P407) and polyethylene glycol 600 (PEG 600). The formulations were characterized using texture analysis (for mechanical and mucoadhesion properties), hydration studies, thermogravimetric analysis (TGA), DSC, X-ray powder diffraction (XRPD) and scanning electron microscopy (SEM). Results and discussion: DSC showed the eutectic temperature (12.8?°C) of the system where the liquid solution and pure solids both existed at a fixed pressure which helped determine the freeze-annealing cycle at 55?°C for 7?h. Mechanical resistance to compression, hydration and mucoadhesion studies showed that optimized wafers were obtained from aqueous gels containing 2% w/w CAR 911, 4% w/w P407 and 4.4% w/w PEG 600. TGA showed residual water of approximately 1% and SEM showed a porous polymeric network that made ease of hydration possible. Conclusions: Lyophilized wafers by freeze-drying gels containing 2% w/w CAR 911, 4% w/w P407 and 4.4% w/w PEG 600 with optimum physico-mechanical properties has been achieved. 相似文献
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