جستجوی مقالات مرتبط با کلیدواژه « dissolution » در نشریات گروه « پزشکی »

The present study mainly aimed to prepare solid dispersions (SDs) of a poorly water-soluble compound, carvedilol (CA), in the presence of pluronic F68 (F68) and myrj 52 by adopting wet milling technique in order to enhance drug dissolution. The process enabled the preparation of SDs without using any toxic organic solvents. SDs with different CA, surfactant ratios were prepared by adopting wet milling followed by freeze-drying method and evaluated for their particle size and dissolution. They were also characterized based on/using X-ray diffraction (XRD), differential scanning calorimetry (DSC), fourier transform infrared (FTIR) spectroscopy, scanning electron microscope (SEM), and saturated solubility. The effect of cryoprotectant type on the dissolution and particle size of SDs was also investigated. Wet milling process resulted in the reduced particle size depending on the type of surfactant. The significant drug dissolution and saturated solubility enhancement were recorded for milled SD formulations. In this regard, Myrj had a greater impact compared to F68. Dissolution efficiencies (DE30) obtained for the myrj-included SDs were up to 8.2-fold higher than that of untreated CA. The type of cryoprotectant was also found to affect the drug dissolution. According to the results, partial amorphization occurred in wet-milled samples, as confirmed by XRD and DSC analysis. It was concluded that using an appropriate surfactant along with wet-milling method may have been an effective approach for improving the dissolution rate of CA, a poorly soluble compound.

 Efavirenz nanosuspensions (EZ-NSs) were developed by the wet milling method as the most promising top-down nanosizing technique. Different process and formulation parameters were studied and optimized to produce appropriate EZ-NS in suitable conditions to enhance drug dissolution.

 In the preliminary studies, various polymeric stabilizers, including Pluronic F68, sodium carboxymethylcellulose (CMC), hydroxypropyl methylcellulose (HPMC), and polyvinyl alcohol (PVA), as well as different sizes and weight of milling beads were used to prepare NSs. The effect of sodium lauryl sulfate (SLS) concentration on the NS properties was also evaluated. The influence of other formulation and process parameters, including polymer concentration, milling speed, and milling time, on the particle size and distribution of NSs were investigated using Box-Behnken design. The optimized freeze-dried nanosuspension was characterized by redispersibility, physicochemical properties, and stability.

 A combination of PVA and SLS was selected as steric and electrostatic stabilizers. The optimum EZ-NS displayed a uniform size distribution with a mean particle size and zeta potential of 254.4 nm and 21.1 mV, respectively. The solidified nanosuspension was well redispersed to the original nanoparticles. Significantly enhanced aqueous solubility (about 11-fold) and accelerated dissolution rate were observed for the optimized formulation. This could be attributed to the reduced particle size and partial amorphization of EZ during the preparation process, studied by X-ray diffraction. Accelerated studies confirmed the stability of the optimum freeze-dried formulation over the examined period of three months.

 Optimization of different variables led to the formation of EZ-NSs with desired properties through wet milling in a very short time compared to the previous study and therefore reduced production costs. This formulation seems to be a suitable approach for solubility and dissolution enhancement of EZ and may have a great potential to improve the drug's oral bioavailability.

Novel cocrystals of nevirapine (NP) were designed and prepared with salicylamide and 3-hydroxy benzoic acid (3-HBA).

The cocrystals were prepared by solvent drop grinding method by adding few drops of acetone to enhance the solubility and dissolution. The drug and cocrystals were characterized by differential scanning calorimetry (DSC) and powder x-ray diffraction (PXRD). The solubility of NP, its wet ground form, and cocrystals were investigated at different pH. Moreover, the effect of surfactant on solubility of cocrystals was also studied. Finally, intrinsic dissolution rate (IDR) and stability of cocrystals was examined.

The characterization of cocrystals by DSC and PXRD revealed formation of new solid forms due to changes in thermogram and PXRD pattern. The cocrystal of NP with 3-HBA showed 4.5 folds greater solubility in pH 1.2 buffer and 5.5 folds in 1% Tween 80 as compared to original drug. IDR of cocrystals was higher than the pure drug in 0.1 N hydrochloric acid (HCl). Moreover, cocrystals were found physically stable after 3 months as evident from unchanged IDR.

Hence, the present research indicates the new stable solid forms of NP with improved dissolution rate than pure drug.

Aimed to improve the dissolution profile of risperidone and increase the compliance of psychotic patients, we designed a fast dissolution tablet (FDT) containing nanoparticles. Risperidone nanoparticles were prepared by the acid-alkali neutralization method, and their size and stability were evaluated. Spray freeze-drying (SFD) process was then employed to fabricate the nanoaggregates using sugars. The physicochemical properties of the dried powders were assessed. Finally, nanoaggregates were compressed into tablets, and their properties were evaluated.The results show that the synergic effect of cremophore EL and hydroxypropyl methyl cellulose E15 can give rise to the formation of risperidone nanosuspension with the particle size of 188 nm. Moreoevr, it is shown that the fabrication of risperidone nanoaggregate enhanced the drug dissolution and decreased that to 2 min, which is faster than coarse risperidone powder (with dissolution time of 60 min). The formulations of FDT containing 9.5% of sodium starch glycolate and 83.2% microcrystalline cellulose were selected with a disintegration time of less than 30 seconds and a dissolution time of 10 minutes. This investigation shows that the preparation of FDT containing nanoparticles using SFD is an easy and feasible method for improving the dissolution profile of many drugs with low solubility.

The objective of the present study was to design a porous osmotic pump-based drug delivery system for the controlled release of captopril (Cap) which can maintain a constant therapeutic concentration, thus reducing dose-related side effects and dosing frequency.

The study evaluated in vitro drug release for the controlled porosity osmotic pump tablet (CPOPT) of Cap. This in vitro drug release study investigated the influence of the tablet formulation variables such as the amount of mannitol, hydroxypropylmethylcellulose K4M (HPMCK4M), and polyvinyl pyrrolidone (PVP K-30) in the core and the concentration of cellulose acetate and polyethylene glycol 400 (PEG-400) in the coating solution.

It was found that the drug release was mostly affected by the amount of mannitol, HPMCK4M, and PVP K-30 in the core and the amount of cellulose acetate and PEG-400 in the coating solution.

In general, the objective of the study was established by coating the core tablet containing osmotic and pore-forming agents. Therefore, the CPOPT of Cap could be a safe, effective, stable, and promising preparation in the future.

Irbesartan (IBS), an angiotensin II receptor (AT1 subtype) antagonist which blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selective binding to AT1 angiotensin II receptor. It belongs to BCS class II drug (low aqueous solubility and high permeability). Improvement of dissolution characteristics of the drug by formulating is being investigated in the current study.

Solid dispersions (SD) formulations were prepared by the melting fusion technique and nanocomposites (NC) were prepared by a single emulsion technique. Eight batches of SD and three batches of NC were formulated in three ratios of drug to polymer (1:1, 1:2, and 1:3). The batches were evaluated for equilibrium solubility studies, Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM), field emission SEM (FESEM), transmission electron microscopy (TEM), and in vitro dissolution studies.

Solubility studies revealed maximum solubility at a 1:2 ratio of solid dispersions and a 1:1 ratio of nanocomposites. No drug-polymer interaction was observed in FTIR results. DSC, SEM, and XRD analysis revealed changes in drug crystallinity i.e. conversion to the amorphous state of drugs. Nanosize of particles in the NC1 batch was confirmed in TEM studies. Solid dispersions and nanocomposites showed significant enhancement of dissolution in comparison to that of the pure drug (100% drug release in approximately 1 hour).

Nanocomposites proved superior carriers to solid dispersions in terms of the dissolution enhancement. Further, in vivo studies indicated that the induction of systolic and diastolic blood pressure in the optimized formulation (NC1) was significantly decreased in comparison to the disease control group (P<0.01) at all time intervals along with pure drug (P<0.05).

Physiologically generated supersaturation and subsequent precipitation of a weakly basic drug in the small intestine leads to compromised bioavailability.

In this work, the pH -induced precipitation of dipyridamole (DPD) as a model weakly basic drug in the presence of Eudragit L100 (Eu) and hydroxypropyl cellulose (HPC) was investigated. Inhibitory effects of the polymers on precipitation of DPD at varying drug/polymer ratios were examined. The effects of the polymers on the DPD dissolution property were assessed using drug/polymer physical mixtures (PMs) and solid dispersions (SDs).

Significant inhibitory effects on precipitation were found using Eu, while HPC as well inhibited precipitation, but to a lower level than found with Eu. The PMs resulted in higher area under the dissolution curve (AUDC) compared to SDs. For SDs, the AUDC was limited by the slow release of the drug from the polymers in acidic pH which in turn decreased supersaturation of DPD following acidic to neutral pH transition.

From these results, it may be supposed that both the ability to create and stabilize supersaturation separately of each other to be important for enhancing dissolution of DPD.

Modafinil (MDF) is used orally for the treatment of attention-deficit/hyperactivity disorder and narcolepsy. It holds low solubility and high permeability; therefore, improving its dissolution properties by preparing nanoformulations can be a promising approach to enhance its oral absorption. Our aims were to prepare and characterize MDF-Eudragit® RS100 (MDF-ERS) nanoparticles by electrospray technique. Electrosprayed nanoparticles were fabricated by varying MDF to ERS ratios and concentrations. The formulations were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier-transform infrared spectroscopy (FTIR). Release studies were performed on nanoparticles, physical mixtures, and raw MDF. The release data were fitted to different models to understand the mechanism of the drug release. Electrospraying of MDF and ERS solution resulted in the preparation of nonobeads or nanofibers, and the particulate characteristics of the obtained products were largely controlled by the polymer amount in the solution. PXRD and thermal analyses showed that MDF was an amorphous phase in the structures of nanoparticles. Using FTIR, no interaction was observed between MDF and ERS in nanoparticles. Nanoparticles showed biphasic release profiles and the order of dissolution rates was: nanofibers>MDF>nanobeads. The well-fitted model was Weibull model, indicating a Fickian diffusion as the main mechanism of release. The results suggest that by optimization of variables such as solution concentration of MDF-ERS nanofibers and nanobeads with higher dissolution rates can be made by electrospray. Electrospray deposition as a simple, continuous, and surfactant free method is an excellent choice for preparation of drug loaded polymeric nanoparticles.

In this study, a novel mesoporous silica nanoparticles drug carrier contributes to improving the solubility, dissolution, and the oral bioavailability of apigenin (AP). The apigenin of solid dispersion of mesoporous silica nanoparticles (AP-MSN) was prepared by physical absorption method and also, in-vitro drug release and in-vivo bioavailability performance were evaluated. Based on its solubility, the AP-MSN solid dispersion was prepared at the weight ratio of 1:1 to obtain the optimum solubility. The loading efficiency (LE), encapsulation efficiency (EE), and solubility of AP-MSN solid dispersion were 29.71%, 42.27%, and 25.11 µg/mL, respectively. SEM, TEM, BET, FTIR, XRD, DSC, and TG were also carried out. These results demonstrated that AP was good absorbed into the pores of MSN through physical absorption effect of MSN. The DMF residues of AP-MSN solid dispersion meet the ICH requirements. It was vital that the AP-MSN solid dispersion behaved well in-vitro and the accumulative release of AP-MSN solid dispersion was 2.37 times higher than that of raw AP. In-vivo study, the AP area under curve0-t was 8.32 times higher for the AP-MSN solid dispersion than that of raw AP, which indicated that the bioavailability of AP-MSN solid dispersion was greatly improved. Therefore, the prepared AP-MSN solid dispersion presents potential as a novel oral therapeutic agent formulation for clinical application.

Triple solid dispersion adsorbates (TSDads) and spherical agglomerates (SA) present new techniques that extensively enhance dissolution of poorly soluble drugs. The aim of the present study is to hasten the onset of hypoglycemic effect of glimepiride through enhancing its rate of release from tablet formulation prepared from either technique. Drug release from TSDads or SA tablets with different added excipients was explored. Scanning electron microscopy (SEM) and effect of compression on dissolution were illustrated. Pharmacodynamic evaluation was performed on optimized tablets. TSDads & SA tablets with Cross Povidone showed least disintegration times of 1.48 and 0.5 min. respectively. Kinetics of drug release recorded least half-lives (54.13 and 59.83min for both techniques respectively). Cross section in tablets displayed an organized interconnected matrix under SEM, accounting for the rapid access of dissolution media to the tablet core. Components of tablets filled into capsules showed a similar release profile to that of tablets after compression as indicated by similarity factor. The onset time of maximum reduction in blood glucose in male albino rabbits was hastened to 2h instead of 3h for commercial tablets. After optimization of tablet excipients that interacted differently with respect to their effect on drug release, we could conclude that both amorphisation and spheronization were equally successful in promoting in vitro dissolution enhancement as well as providing a more rapid onset time for drug action in vivo.

A comparative study was carried out between surface solid dispersion (SSD) and solid dispersion (SD) of meloxicam (MLX) to assess the solubility and dissolution enhancement approach and thereafter develop as patient friendly orodispersible tablet. Crospovidone (CPV), a hydrophilic carrier was selected for SSD preparation on the basis of 89% in- vitro MLX adsorption, 19% hydration capacity and high swelling index. SD on the other hand was made with PEG4000. Both were prepared by co-grinding and solvent evaporation method using drug: carrier ratios of 1:1, 1:4, and 1:8. Formulation SSDS3 (MLX: CPV in 1:8 ratio) made by solvent evaporation method showed t50% of 28 min and 80.9% DE50min which was higher in comparison to the corresponding solid dispersion, SDS3 (t50% of 35min and 76.4% DE50min). Both SSDS3 and SDS3 were developed as orodispersible tablets and evaluated. Tablet formulation F3 made with SSD3 with a disintegration time of 11 secs, by wetting time= 6 sec, high water absorption of 78%by wt and cumulative drug release of 97% proved to be superior than the tablet made with SD3. Conclusively, the SSD of meloxicam has the potential to be developed as fast acing formulation that can ensure almost complete release of drug.

Cocrystallisation of drug with coformers is a promising approach to alter the solid sate properties of drug substances like solubility and dissolution. The objective of the present work was to prepare, formulate and evaluate the piroxicam cocrystal by screening various coformers.
Cocrystals of piroxicam were prepared by dry grinding method. The melting point and solubility of crystalline phase was determined. The potential cocrystal was characterized by DSC, IR, XRPD. Other pharmaceutical properties like solubility and dissolution rate were also evaluated. Orodispersible tablets of piroxicam cocrystal were formulated, optimized and evaluated using 32 factorial design.
Cocrystals of piroxicam-sodium acetate revealed the variation in melting points and solubility. The cocrystals were obtained in 1:1 ratio with sodium acetate. The analysis of Infrared explicitly indicated the shifting of characteristic bands of piroxicam. The X-Ray Powder Diffraction pattern denoted the crystallinity of cocrystals and noteworthy difference in 2θ value of intense peaks. Differential scanning calorimetry spectra of cocrystals indicated altered endotherms corresponding to melting point. The pH solubility profile of piroxicam showed sigmoidal curve, which authenticated the pKa-dependent solubility. Piroxicam cocrystals also exhibited a similar pH-solubility profile. The cocrystals exhibited faster dissolution rate owing to cocrystallization as evident from 30% increase in the extent of dissolution. The orodispersible tablets of piroxicam cocrystals were successfully prepared by direct compression method using crosscarmelose sodium as superdisintegrant with improved disintegration time (30 sec) and dissolution rate.
The piroxicam cocrystal with modified properties was prepared with sodium acetate and formulated as orodispersible tablets having faster disintegration and greater dissolution rate.

Ezetimide belongs to a class of lipid lowering compounds that selectively inhibits intestinal absorption of cholesterol and related phytosterols. The purpose of this study is to establish a reliable and quick method for the assignment of ezetimibe in tablets form by high performance liquid chromatography with ultraviolet detection (HPLC-UV). A rapid and sensitive HPLC method has been developed for determination of ezetimibe in tablets formulation. Mobile phase was composed of acetonitrile-ammonium acetate (10 mM, pH 3.0), 75:25 (v/v) with a flow rate of 1 ml/min. The eluted peaks were detected by a UV detector was set at wavelength of 240 nm. The method results in excellent separation with good resolution of analyte. Standard curves were linear (r = 0.996) over the wide ezetimibe concentration range of 10-60.0 µg mL-1 with acceptable accuracy and precision. The limits of detection (LOD) and quantitation (LOQ) of the method were 5 and 10 µg/ml, respectively. The average drug recovery was 95.3% throughout the linear concentration range. Statistical assessment of various in vitro dissolution parameters and assay results was also conducted to establish if there were any significant difference among them. The validated HPLC method has been used successfully to study ezetimibe. Due to simplicity, rapidity and accuracy of the method, we believe that the method will be useful for routine quality control analysis.

The aim of present study was to improve the dissolution rate of poorly soluble drug Loperamide (LPM) by liquisolid compact technique.
Liquisolid compacts of LPM were prepared using Propylene glycol (PG) as a solvent, Avicel pH 102 as carrier, Aerosil as coating material and Sodium Starch Glycolate (SSG) as superdisintegrant. Interactions between the drug and excipients were examined by Fourier Transform Infrared (FTIR) spectroscopy. The dissolution studies for LPM liquisolid formulation, marketed product and pure drug were carried out in pH 1.2 HCl buffer as dissolution media.
Results confirmed the absence of chemical interactions between the drug and excipients. From the solubility studies, it was observed the LPM was highly soluble in PG thereby it was selected as a solvent. The dissolution efficiency of LPM at 15 min was increased from 9.99 % for pure drug and 54.57% for marketed product to 86.81% for the tablets prepared by liquisolid compact technique. Stability studies showed no significant change in percent cumulative drug release, hardness, disintegration time, friability and drug content for 3 months.
Formulation F2 showed significant increase in dissolution rate compared to the marketed product at pH 1.2 where LPM is largely absorbed. Around 90% of the drug was released from F2 in 30 min compared to the marketed product and it might be due to the increased wetting and surface area of the particles. Hence, the liquisolid compact technique appears to be a promising approach for improving the dissolution rate of poorly soluble drug.

Tolterodine tartrate, is a new, potent and competitive muscarinic receptor antagonist in clinical development for the treatment of urge incontinence and other symptoms of unstable bladder. The purpose of this study is to establish a reliable and quick method for the assignment of tolterodine tartrate by high performance liquid chromatography with ultraviolet detection (HPLC-UV). A rapid and sensitive high performance liquid chromatographic (HPLC) method has been developed for determination of tolterodine tartrate. Mobile phase was composed of phosphate acetate 0.1 M (pH 2.5)-acetonitrile (50:50 v/v) with a flow rate of 1.2 ml/min. The eluted peaks were detected by a UV detector was set at wavelength of 285 nm. The method was validated in the range of tolterodine tartrate concentrations from 10 to 100 µg/ml. The limits of detection (LOD) and quantitation (LOQ) of the method were 5 and 10 µg/ml, respectively. The average drug recovery was 98.20 % throughout the linear concentration range. The average within-run and between-run accuracy values of 98.56 % and 99.11 % respectively. Statistical assessment of various in vitro dissolution parameters and assay results was also conducted to establish if there were any significant difference among them. The validated HPLC method has been used successfully to study tolterodine tartrate.

Imatinib mesylat as an oral anticancer agent need a controlled released formulation to get steady and stable plasma concentration. The aim of the present study was to develop controlled release matrix tablet formulations of Imatinib using hydroxy propyl methyl Cellulose as a hydrophilic release retardant polymer and to study the effects of different formulation features like polymer viscosity grade, ratio of the polymer, compression force, and release medium on the in vitro release properties. The in vitro release studies were performed using US Pharmacopoeia type I apparatus. The release kinetics was analyzed by Korsmeyer–Peppas model and were also analyzed using statistical method and f2 metric values. The release profiles look like Higuchi’s square root kinetics model irrespective of the viscosity grade and polymer proportion. The results showed that the release rate of the drug is greatly affected by the drug/polymer ratio and viscosity grade. Also, the effect of release medium and compression force was showed to be significant on the release profiles. The release mechanism was found to be anomalous non-Fickian diffusion in all formulations. The formulations were found to be reproducible and stable. Controlled release formulations were developed with different release rates and profiles so that these formulations could be evaluated for more in vivo studies.

Solid dispersions have been efficient in improving the dissolution rate and bioavailability of hydrophobic drugs. The aim of the present study was enhancement of the dissolution profile of Spironolactone using solid dispersion. Spironolactone solid dispersions (1:1, 1:2 and 2:1 drug: carrier weight ratio) were prepared by polyethylene glycol (PEG) 6000 as a carrier by hot melt method. The influence of several amounts of Tween 20, 60, and 80 were also studied. The dissolution profile was evaluated by USP Apparatus II. The results showed that solid dispersions were efficacious to enhance the dissolution rate of Spironolactone in water; and the procedure indicated that there was an increase in dissolution rate for solid dispersions containing the surfactant Tweens. The solid dispersions were evaluated using Fourier-transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD) and Differential Scanning Calorimetry (DSC) studies; and the results showed no complex formation or change in crystal shape of drug. It is concluded that solid dispersion technique can be successfully used for improvement of dissolution of Spironolactone.

The main objective of the current research work was to formulate and evaluate furosemide loaded silica lipid hybrid microparticles for improved oral delivery. A novel silica-lipid hybrid microparticulate system is used for enhancing the oral absorption of low solubility and low permeability of (BCS Class IV) drugs. Silica-lipid hybrid microparticles include the drug solubilising effect of dispersed lipids and stabilizing effect of hydrophilic silica particles to increase drug solubilisation, which leads to enhanced oral bioavailability. The slica lipid hybrid (SLH) microparticles were composed of poorly soluble drug (furosemide), dispersion of oil phase (Soya bean oil and miglyol) in lecithin (Phospholipoid 90H), non-ionic surfactant (Polysorbate 80) and adsorbent (Aerosol 380). Saturation solubility studies were performed in different oils and surfactants with increased concentration of drug revealed increased solubility of furosemide. In vitro dissolution studies conducted under simulated gastric medium revealed 2 4 fold increase in dissolution efficiencies for SLH microparticles compared to that of pure drug (furosemide) and marketed formulation Lasix®. Ex vivo studies showed enhanced lipid digestibility, which improved drug permeability. Solid-state characterization of SLH microparticles by X-ray powder diffraction and Fourier transform infrared spectroscopic analysis confirmed non-crystalline nature and more compatibility of furosemide in silicalipid hybrid microparticles. It can be concluded that the role of lipids and hydrophilic silica based carrier highlighted in enhancing solubility and permeability, and hence the oral bioavailability of poorly soluble drugs.

The purpose of the present investigation was to increase the solubility and dissolution rate of celecoxib (CLX) by preparing microcrystals of drug by solvent change precipitation. This procedure was optimized in order to obtain stable and homogeneous particles with a small particle size, high yield and fast dissolution rate. CLX agglomerates were prepared with brij35 (stabilizer agent) using acetone as solvent, water as non-solvent, respectively. The agglomerates were characterized by DSC, XRD, FTIR studies. A full-factorial design was employed to study the effect of independent variables, the amounts of stirring rate (X1), volume of organic solvent (X2), volume of aqueous solvent (X3), time of stirring (X4), concentration of Brij (X5), concentration of Tween 80 (X6), concentration of HPMC (X7) on dependent variables, particle size (PS), drug content (DC), drug released after 15 min (Q15), crystal yield (CY), Gibbs free energy change (ΔG°tr), antalpy change (ΔH) and saturated solubility (Ss). The DSC and FTIR results indicated the absence of any interactions between drug and stabilizers. These studies showed a decrease in crystalinity in agglomerates. The crystals exhibited significantly improved micromeritic properties compared to pure drug. The drug content and crystal yield were in the range of 32.84-48.22% and 64.55-83.33% with all formulations, respectively. The solubility and drug release rates increased with an increase in concentration of stabilizer. The results show that microcrystals of the drug in stabilizer considerably enhanced the dissolution rate.