Formulation and evaluation of Fluconazole Nanosuspensions: In vitro characterization and transcorneal permeability studies.

The aim in this study was to develop and evaluate a nanofluconazole (FLZ) formulation with increased solubility and permeation rate using nanosuspensions. The FLZ nanosuspensions were stabilized using a variety of stabilizing agents and surfactants in various concentrations. The FLZ nanosuspension was characterized in vitro using particle size, zeta potential, X-ray powder diffraction (XRPD), and solubility. In addition, the ex vivo ocular permeation of FLZ through a goat cornea was analyzed. The results showed that the particle size of all nanosuspension formulations was in the nanometer range from 174.5 ± 1.9 to 720.2 ± 4.77 nm; that of the untreated drug was 18.34 µm. The zeta potential values were acceptable, which indicated suitable stability for formulations. The solubility of the nanosuspensions was up to 5.7-fold higher compared with that of the untreated drug. The results of the ex vivo ocular diffusion of the FLZ nanosuspensions showed the percentage of FLZ penetrating via the goat cornea increased after using Kollicoat to stabilize the nanosuspension formulation. Consequently, when using a nanosuspension formulation of Kollicoat, the antifungal activity of the drug strengthens.

Optimization and evaluation of Lisinopril mucoadhesive sustained release matrix pellets: In-vitro and ex-vivo studies.

Lisinopril (LIS) is antihypertensive drug, classified as a class III drug with high water solubility and low permeability. To overcome the low permeability, 32 factorial designs aimed to formulate LIS as a sustained-release (LIS-SR) matrix pellet by extrusion/spheronization. Matrix pellets were composed of wet mass containing Avicel® and polymeric matrix polymers (sodium alginate (SA) and chitosan (CS)). Evaluation of the effect of two independent variables, matrix-forming units (SA and CS) on mean line torque, on pellet size, dissolution rate after 6 h, and mucoadhesion strength of the pellets were assessed using Statgraphics software. The tested formulations (F1-F9) showed that mean line torque ranged from 1.583 to 0.461 Nm, with LIS content in the LIS-SR pellets ranged from 87.9 to 103%, sizes varied from 1906 to 1404 µm and high percentages of drug released from pellets formulations (68.48 to 74.18 %), while the mean zeta potential value of mucoadhesive range from -17.5 to -22.9 mV. The selection of optimized formulation must have the following desirability: maximum peak torque, maximum pellets' particle size, and minimum % LIS release after 6hr. LIS optimized sustained release pellet formula composed of 2,159 % SA and 0.357 % CS was chosen as optimized formula. It's showed a 1.055 Nm mean line torque was responsible for the increased pellet size to 1830.8 µm with decreased release rate 56.2 % after 6 hr, and -20.33 mV average mucin zeta potential. Ex-vivo mucoadhesion studies revealed that that the optimize formulation, exhibited excellent mucoadhesive properties, after 1 h, about 73% of the pellets were still attached to the mucus membrane. Additionally, ex-vivo permeation determination of LIS from the optimized LIS-SR formulation was found to be significantly higher (1.7-folds) as compared to free LIS. In conclusion: LIS-SR matrix pellets, prepared with an extrusion/spheronization have desirable excellent characteristics in-vitro and ex-vivo sustained-release pellet formulation of LIS-SR was able to sustain the release of LIS for up to 8 h.

Optimization and evaluation of venlafaxine hydrochloride fast dissolving oral films.

Three factors, three levels (33) full factorial design was used to develop venlafaxine HCl fast dissolving oral films (FDOFs) to optimize the concentrations of the film forming polymer; hydroxypropyl methylcellulose HPMC (X1), superdisintegrant; sodium starch glycolate SSG, (X2) and glycerol as the film plasticizer (X3). Effects of the three factors on the disintegration time (Y1), swelling index (Y2), and dissolution efficiency at 15 min; DE%15 (Y3) of the prepared FDOFs were evaluated by using statistical models. The optimized film formula was characterized in term of x-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and morphological characteristics. Disintegration time was found to increase with the increase in HPMC (X1) concentration, and the shortest disintegration time (21.67 ± 2.08 s) was observed in case of F2 formula (lowest HPMC level and highest glycerol level in absence of SSG). The highest swelling index (3.64 ± 0.59) was observed in case of film formula F1 (medium concentrations of both HPMC and glycerol and highest SSG concentration. The results also indicated that as the concentration of HPMC increased the DE%15 decreased. SSG (X2), with highest value (72.33 ± 1.71%) was recorded for in case of F12 (using 2% HPMC, 5%SSG and 1.5% glycerol). The optimized FDOF formula derived by the statistical models suggested 2% HPMC, 5% SSG, and 1% glycerol. The data obtained from DSC and XRPD revealed no interaction between drug and FDOT excipients. In addition, XRPD studies proved that the venlafaxine HCl was homogeneously dispersed in the film matrix.

Application of a quality-by-design approach for utilizing sodium stearyl fumarate as a taste-masking agent in dextromethorphan hydrobromide orally disintegrating tablets.

Orally dissolving tablets (ODTs) represent one of the recent advances in drug delivery. The foremost objective of this study was to optimize the utilization of lubricant sodium stearyl fumarate in the preparation of dextromethorphan hydrobromide ODTs with enhanced taste-masking properties. The simple blending of sodium stearyl fumarate with the powder bed would result in taste-masking through physical adsorption of the lubricant particles on the drug particles. A randomized 32 full factorial experimental design was used to characterize the relationship between lubricant ratio (X1), mixing time (X2), and the tablet properties. The tablets were assessed for friability, hardness, disintegration time, and in-vitro dissolution. All tablets showed hardness within the range of 3.0-3.7 kp, and the % loss in friability test was less than 1.1%. The in-vitro disintegration time ranged between 9 and 25 s. An in-vitro drug release study of the prepared ODTs showed that more than 90% of the drug was released within 30 min. A palatability test of the optimized formula conducted in human volunteers showed acceptable taste and mouthfeel with in-vivo disintegration time of 17 s. Thus, results obtained convincingly showed successful fast disintegration of the prepared tablets and acceptable palatability when using sodium stearyl fumarate as a taste masking agent.

Physicochemical and pharmacodynamic evaluation of pioglitazone binary systems with hydrophilic carriers.

Pioglitazone (PGZ) is an antidiabetic agent belongs to thiazolidinediones. Binary systems of PGZ in the matrices of kollicoat IR (KL) and gelucire (GL) at different weight ratios were prepared by kneading and co-evaporation methods, respectively. The drug solid dispersions were characterized in terms of in vitro dissolution studies, differential scanning calorimetry (DSC), and X-ray powder diffraction (XRPD). The effects of PGZ-KL (1:4) solid dispersion on the body weight, blood glucose, renal and hepatic functions of the diabetic rats were evaluated. Enhanced drug dissolution was observed in the case of PGZ-KL binary systems depending on the drug to polymer weight ratio. A reduction of 39.7, 32.7 and 26.6% for diabetic control, PGZ untreated and PGZ-KL (1:4), respectively, was recorded after 2 weeks. PGZ-KL (1:4) solid dispersion also showed significantly lower glucose blood level (p < 0.05) compared to the diabetic control group along the period of experiment. The level of ALT was highly significantly decreased in the animal group treated with PGZ-KL solid dispersion (p < 0.001). However, treatment of diabetic rats with either PGZ-KL or PGZ untreated significantly reduced the level of creatinine compared to the diabetic control and the difference between them was non-significant.

Physicochemical, pharmacokinetics, and histological evaluation of new naproxen-quercetin co-lyophilizate to diminish drug-induced gastric irritations in rats.

Quercetin (QUE) is a flavonoid found in several plants and commonly distributed in edible vegetables and fruits. To evaluate the effect of co-lyophilization of naproxen (NPX) with QUE at different weight ratios on physicochemical characteristics induced gastric irritation, and drug pharmacokinetics. NPX binary systems with QUE in different weight ratios were prepared by freeze-drying alkalinized solutions, and were characterized in terms of physicochemical properties as well as NPX dissolution rate in acidic pH. NPX-induced gastric inflammation studies were carried out in rats for 7 days. The pharmacokinetics of the two formulations were assessed to evaluate the bioavailability of NPX-QUE 1:2 co-lyophilizate. Westar rats were administered oral doses equivalent to 40 mg kg-1 of NPX and blood samples were taken from the retro-orbital vein of rats at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0 12.0, and 24.0 h post dosing. Co-lyophilization of NPX with QUE enhanced drug dissolution rate in the acidic medium, which was correlated with an increased QUE weight ratio in the co-lyophilizates. Rat stomachs from group V (NPX-QUE 1:2 co-lyophilizate) showed non-significant changes, and biopsies from this group showed no significant leukocyte infiltration and edema in the mucosa. The bioavailability of NPX-QUE 1: 2 co-lyophilizate was similar to the control sample. NPX-QUE 1: 2 co-lyophilizate could be an alternative to NPX in the treatment of arthritis as it minimizes the potential for gastric irritation and enhances safety while retaining the same efficacy and bioavailability.

Optimized furosemide taste masked orally disintegrating tablets.

Optimized orally disintegrating tablets (ODTs) containing furosemide (FUR) were prepared by direct compression method. Two factors, three levels (32) full factorial design was used to optimize the effect of taste masking agent (Eudragit E100; X1) and superdisintegarant; croscarmellose sodium (CCS; X2) on tablet properties. A composite was prepared by mixing ethanolic solution of FUR and Eudragit E100 with mannitol prior to mixing with other tablet ingredients. The prepared ODTs were characterized for their FUR content, hardness, friability and wetting time. The optimized ODT formulation (F1) was evaluated in term of palatability parameters and the in vivo disintegration. The manufactured ODTs were complying with the pharmacopeia guidelines regarding hardness, friability, weight variation and content. Eudragit E100 had a very slightly enhancing effect on tablets disintegration. However, the effects of both Eudragit E100 (X1) and CCS (X2) on ODTs disintegration time (Y1) were insignificant (p > 0.05). Moreover, X1 exhibited antagonistic effect on the dissolution after 5 and 30 min (D5 and D30, respectively), but only its effect on D30 is significant (p = 0.0004). Furthermore, the optimized ODTs formula showed good to acceptable taste in term of palatability, and in vivo disintegration time of this formula was about 10 s.

Tenoxicam-kollicoat IR binary systems: physicochemical and biological evaluation.

Tenoxicam (TNX) binary systems in Kollicoat IR (KL) matrix were prepared in different drug: polymer ratios using kneading and spray-drying method. The prepared binary systems were characterized for drug dissolution rate, differential scanning calorimetry (DSC), IR spectroscopy and x-ray diffractometry. The results showed that the drug dissolution rate was remarkably enhanced by incorporating it in the KL matrix either by kneading or spray-drying, and the dissolution rate was increased by decreasing the drug weight ratio. The DSc and x-ray studies revealed the presence of TNX in less crystalline or amorphous state in its-KL binary systems. Moreover, the spray-dried TNX-KL system in 1:4 ratio, that exhibited the faster dissolution rate, was formulated in oral disintegrating tablets (ODTs). The data indicated that a fast disintegration and higher drug dissolution rate was achieved in case of the ODTs containing the spray-dried form compared to the ODTS containing untreated drug or the commercial tablet (Epicotil). Also, the drug exhibited significantly (p < 0.01) faster onset of the anti-inflammatory analgesic activities in case of the ODTs containing the spray-dried form, that was superior to that observed with both the commercial tablet product and the ODTS containing untreated drug.

Formulation of immediate release pellets containing famotidine solid dispersions.

Famotidine (FM) is a potent H2-receptor antagonist used for the treatment of peptic ulcer. It has a low and variable bioavailability which is attributed to its low water solubility. In this study, the dissolution of the drug was enhanced by a preparation of solid dispersion using two hydrophilic carriers, namely Gelucire 50/13 and Pluronic F-127. The prepared solid dispersions were characterized by differential scanning calorimetry (DSC), which indicated that there were no signs of interaction of the drug with the carriers used in the case of solid dispersions containing higher polymeric contents (1:3 and 1:5). FM solid dispersions in the matrices of Gelucire 50/13 and Pluronic F-127 (1:3) were used to prepare pellets. The scanning electron microscope (SEM) images of pellets showed that the pellets have spherical shape and their size depends on the carrier used. The dissolution of the drug from either solid dispersion or pellets was performed. The dissolution study depicted that, the presence of the drug in solid dispersion enhanced its dissolution in comparison with the drug itself. Also, the drug release from the manufactured pellets was found to be improved in the case of solid dispersions (drug:carrier 1:3). A complete drug release occurred after 30 min from pellets containing solid dispersions, while only about 30% of the loaded FM was released from pellets containing untreated drug after 2 h.

Utilization of Waste Eggshell Powder as an Excipient for Vitamin D3 Tablet Preparation.

Keeping in mind the health scenario in Kingdom of Saudi Arabia with respect to vitamin D3 (VD3) deficiency and its significant role in calcium homeostasis and human metabolism, this research is exploring the combination of eggshell (as a source of calcium) and VD3 as a very economical solution for this problem. Eggshells from local restaurant were collected, washed, ground, sieved, and characterized by Fourier transforms infrared spectroscopy (FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Brunauer-Emmett-Teller (BET) techniques. The results of FTIR, SEM, DSC, XRD, and BET indicate that eggshell powder (ESP) was properly processed. Directly compressed tablets containing 2.5 mg of VD3 (equivalent to 50,000 IU), that are based on the use of ESP as tablet filler, were manufactured based on mixing Avicel PH 101 with ESP in different ratios (9:1, 1:1, and 1:9) in addition to the use of both Avicel PH 101 and ESP alone as tablet filler. Tablets properties were evaluated according to USP30-NF25 pharmacopoeia tests in terms of weight variation test, drug content uniformity, tablet hardness, tablet friability, tablet disintegration, and in vitro dissolution profile. The VD3 contents were found to be 98.77-102.35% in all formulations. After 90 min of study, all formulations showed in vitro drug release content in the range of 99.29-101.05%. All of the tested parameters of ESP tablets were similar to those of commercial Avicel PH 101. All of the tested properties of tablets with ESP as a filler were found to be within the acceptable limits of the pharmacopeia recommendations. Therefore, ESP could be exploited for its use as a filler in direct compression tablets.

Optimization of synthesis parameters for mesoporous shell formation on magnetic nanocores and their application as nanocarriers for docetaxel cancer drug.

In this work, Fe3O4@SiO2 nanoparticles were coated with mesoporous silica shell by S-N+I- pathway by using anionic surfactant (S-) and co-structure directing agent (N+). The role of co-structure directing agent (CSDA) is to assist the electrostatic interaction between negatively charged silica layers and the negatively charged surfactant molecules. Prior to the mesoporous shell formation step, magnetic cores were coated with a dense silica layer to prevent iron oxide cores from leaching into the mother system under any acidic circumstances. However, it was found that both dense and mesoporous coating parameters affect the textural properties of the produced mesoporous silica shell (i.e., surface area, pore volume and shell thickness). The synthesized Fe3O4@SiO2@m-SiO2 (MCMSS) nanoparticles have been characterized by low-angle X-ray diffraction, transmission electron microscopy (TEM), and N2 adsorption-desorption analysis, and magnetic properties. The synthesized particles had dense and mesoporous silica shells of 8-37 nm and 26-50 nm, respectively. Furthermore, MCMSS possessed surface area of ca. 259-621 m2·g-1, and pore volume of ca. 0.216-0.443 cc·g-1. MCMSS showed docetaxcel cancer drug storage capacity of 25-33 w/w% and possessed control release from their mesochannels which suggest them as proper nanocarriers for docetaxcel molecules.

Development and optimization of dextromethorphan hydrobromide oral disintegrating tablets: effect of formulation and process variables.

Orally disintegrating tablets (ODTs), which disintegrate rapidly (<1 min) in the mouth and do not require water for administration, have become a very popular dosage form. The study aims to develop a simple and inexpensive method of manufacturing ODTs of a sparingly water-soluble drug, Dextromethorphan hydrobromide. Two factors, three levels (3(2)) full factorial design was used to optimize the diluent, microcrystalline cellulose (X(1)) and superdisintegrant, croscarmellose sodium (X(2)) concentrations. Disintegration time, hardness and T(50) values for all the formulations varied from 12.5 to 152.6 s, 3.58 to 4.92 kp and 0.8 to 2.8 min, respectively. The results indicated that the selected variables have a strong influence on disintegration time, hardness and T(50) of the ODTs. The manufactured ODTs formula composed of 30% microcrystalline cellulose in combination with 3% croscarmellose sodium was chosen as optimized formula, as it showed the lowest disintegration time (12.5 ± 1.22 s), low T(50) (0.8 min.) and hard tablets (4.92 ± 0.28 kp) amongst other tested ODTs formulations. Hardness of DM ODTs was not affected by changing the type of superdisintegrant and lubricant. The disintegration time was significantly (p < 0.05) increased by using sodium starch glycolate instead of croscarmellose sodium.

Optimization of Bromocriptine-Mesylate-Loaded Polycaprolactone Nanoparticles Coated with Chitosan for Nose-to-Brain Delivery: In Vitro and In Vivo Studies.

Bromocriptine mesylate (BM), primarily ergocryptine, is a dopamine agonist derived from ergot alkaloids. This study aimed to formulate chitosan (CS)-coated poly ε-caprolactone nanoparticles (PCL NPs) loaded with BM for direct targeting to the brain via the nasal route. PCL NPs were optimized using response surface methodology and a Box-Behnken factorial design. Independent formulation parameters for nanoparticle attributes, including PCL payload (A), D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) concentration (B), and sonication time (C), were investigated. The dependent variables were nanoparticle size (Y1), zeta potential (Y2), entrapment efficiency (EE; Y3), and drug release rate (Y4). The optimal formulation for BM-PCL NPs was determined to be 50 mg PCL load, 0.0865% TPGS concentration, and 8 min sonication time, resulting in nanoparticles with a size of 296 ± 2.9 nm having a zeta potential of -16.2 ± 3.8 mV, an EE of 90.7 ± 1.9%, and a zero-order release rate of 2.6 ± 1.3%/min. The optimized BM-PCL NPs were then coated with CS at varying concentrations (0.25, 0.5, and 1%) to enhance their effect. The CS-PCL NPs exhibited different particle sizes and zeta potentials depending on the CS concentration used. The highest EE (88%) and drug load (DL; 5.5%) were observed for the optimized BM-CS-PCL NPs coated with 0.25% CS. The BM-CS-PCL NPs displayed a biphasic release pattern, with an initial rapid drug release lasting for 2 h, followed by a sustained release for up to 48 h. The 0.25% CS-coated BM-CS-PCL NPs showed a high level of permeation across the goat nasal mucosa, with reasonable mucoadhesive strength. These findings suggested that the optimized 0.25% CS-coated BM-CS-PCL NPs hold promise for successful nasal delivery, thereby improving the therapeutic efficacy of BM.

Fabrication of mesoporous silica shells on solid silica spheres using anionic surfactants and their potential application in controlling drug release.

In this work, mesoporous shells were constructed on solid silica cores by employing anionic surfactante. A co-structure directing agent (CSDA) has assisted the electrostatic interaction between negatively charged silica particles and the negatively charged surfactant molecules. Synthetic parameters such as reaction time and temperature had a significant impact on the formation of mesoporous silica shelld and their textural properties such as surface area and pore volume. Core-mesoporous shell silica spheres were characterized by small angle X-ray scattering, transmission electron microscopy, and N(2) adsorption–desorption analysis. The synthesized particles have a uniformly mesoporous shell of 34–65 nm and possess a surface area of ca. 7–324 m2/g, and pore volume of ca. 0.008–0.261 cc/g. The core-mesoporous shell silica spheres were loaded with ketoprofen drug molecules. The in vitro drug release study suggested that core-mesoporous shell silica spheres are a suitable nanocarrier for drug molecules offering the possibility of having control over their release rate.

Development and Characterization of Eudragit-RL-100-Based Aceclofenac Sustained-Release Matrix Pellets Prepared via Extrusion/Spheronization.

Aceclofenac (AC) is a nonsteroidal anti-inflammatory drug used in the treatment of chronic pain in conditions such as rheumatoid arthritis, with frequent administration during the day. The formulation of sustained release matrix pellets can provide a promising alternative dosage form that controls the release of the drug, with less blood fluctuation and side effects-especially those related to the gastric system. The extrusion/spheronization technique was used to formulate AC matrix pellets. The response surface methodology (version 17.2.02.; Statgraphics Centurion) was used to study the impacts of Eudragit RL 100 and PVP K90 binder solution concentrations on the pellets' wet mass peak torque, pellet size, and the release of the drug. Statistically, a significant synergistic effect of PVP K90 concentration on the peak torque and pellet size was observed (p = 0.0156 and 0.031, respectively), while Eudragit RL 100 showed significant antagonistic effects (p = 0.042 and 0.013, respectively). The peak torque decreased from 0.513 ± 0.022 to 0.41 ± 0.021 when increasing the Eudragit RL 100 from 0 to 20%, and the pellet size decreased from 0.914 ± 0.047 to 0.789 ± 0.074 nm. The tested independent factors did not significantly affect the drug release in the acidic medium within 2 h, but these pellet formulae maintained the drug release at less than 10% in the acidic medium (pH 1.2), which may decrease gastric irritation side effects. In contrast, a highly significant synergistic effect of Eudragit and highly antagonistic effect of the PVP solution on drug release in the alkaline-pH medium were observed (p = 0.002 and 0.007, respectively). The optimized pellet formula derived from the statistical program, composed of 3.21% Eudragit and 5% PVP solution, showed peak torque of 0.861 ± 0.056 Nm and pellet size of 1090 ± 85 µm, and resulted in a significant retardation effect on the release after 8 h compared to the untreated drug.

Prednisolone-loaded PLGA microspheres. in vitro characterization and in vivo application in adjuvant-induced arthritis in mice.

This study aimed at preparation of a sustained-release steroidal treatment for chronic inflammatory conditions, such as rheumatoid arthritis. To achieve such a goal, biodegradable poly-lactide-co-glycolide prednisolone-loaded microspheres were prepared using o/w emulsion solvent evaporation method. Formulation parameters were adjusted so as to optimize the microsphere characteristics. The prepared microspheres exhibited smooth and intact surfaces, with average size range not exceeding 65 microm. The encapsulation efficiency percent of most microsphere formulations fell within the range of 25-68%. Drug release from these microspheres took place over 4 weeks, with near-to-zero-order patterns. Two successful formulations were chosen for the treatment of unilateral arthritis, induced in mice using Freund's complete adjuvant (FCA). Inflammatory signs of adjuvant arthritis included severe swelling of the FCA-injected limbs, in addition to many histopathological lesions. These included inflammatory cell infiltration, synovial hyperplasia, cartilage, and bone erosion. Parenteral administration of the selected formulae dramatically reduced the swelling of the FCA-injected limbs. In addition, histological examination revealed that the microsphere treatment protocol efficiently protected cartilages and bones of mice, injected with FCA initial and booster doses, from erosion. These results could not be achieved by a single prednisolone dose of 5 mg/kg.

Self-nanoemulsifying ramipril tablets: a novel delivery system for the enhancement of drug dissolution and stability.

Background: Ramipril (RMP) suffers from poor aqueous solubility along with sensitivity to mechanical stress, heat, and moisture. The aim of the current study is to improve RMP solubility and stability by designing solid self-nanoemulsifying drug delivery system (S-SNEDDS) as tablet. Methods: The drug was initially incorporated in different liquid formulations (L-SNEDDS) which were evaluated by equilibrium solubility, droplet size, and zeta potential studies. The optimized formulation was solidified into S-SNEDDS powder by the adsorbent Syloid® and compressed into a self-nanoemulsifying tablet (T-SNEDDS). The optimized tablet was evaluated by drug content uniformity, hardness, friability, disintegration, and dissolution tests. Furthermore, pure RMP, optimized L-SNEDDS, and T-SNEDDS were enrolled in accelerated and long-term stability studies. Results: Among various liquid formulations, F5 L-SNEDDS [capmul MCM/transcutol/HCO-30 (25/25/50%w/w)] showed relatively high drug solubility, nano-scaled droplet size, and high negative zeta potential value. The optimized SNEDDS solidification with Syloid® at ratio (1:1) resulted in a compressible powder with an excellent flowability. The optimized tablet (T-SNEDDS) showed accepted content uniformity, hardness, friability, and disintegration time (<15 minutes). The optimized L-SNEDDS, S-SNEDDS, and T-SNEDDS showed superior enhancement of RMP dissolution compared to the pure drug. Most importantly, T-SNEDDS showed significant (P<0.05) improvement of RMP stability compared to the pure drug and L-SNEDDS in both accelerated and long-term stability studies. Conclusion: RMP-loaded T-SNEDDS offers a potential oral dosage form that provides combined improvement of RMP dissolution and chemical stability.

A Validated Ultra-Performance Liquid Chromatography Tandem Triple Quadrupole Mass Spectrometric Method for Fast Determination of Losartan in Rabbit Plasma.

A rapid UPLC-MS-MS method was developed and validated for determination of losartan in rabbit plasma. Protonated adducts of losartan and eprosartan (IS) were monitored in multiple reaction monitoring mode. Molecular masses of daughter species of losartan were m/z 423.19 > 207 and m/z 423.19 > 180; and of eprosartan were m/z 425.11 > 135 and m/z 425.11 > 107. Losartan from plasma samples was extracted by protein precipitation method. The mobile phase comprising water (0.1% formic acid) (A) and acetonitrile (0.1% formic acid) (B) was used in gradient mode. Analytes were eluted on Acquity UPLC®BEH C18 1.7 µm, 2.1 × 50 mm column. Sample run time was 3.0 min. The validation parameters: accuracy, precision and recovery were within recommended limits. Losartan as well as internal standard remains stable in benchtop stability study as well as in post-preparative stability study. Pharmacokinetic parameters such as Cmax (182.79 ± 23.80 ng/mL), Tmax (1.16 ± 0.28 h), AUC0-t (1188.57 ± 404.60 ng h/mL) and Kel (0.0954 ± 0.0140 h-1) of losartan were measured. Method was successfully applied for pharmacokinetic investigation in rabbits and can be used for losartan determination in plasma sample obtained from other animals.

Stability of insulin during the erosion of poly(lactic acid) and poly(lactic-co-glycolic acid) microspheres.

In recent years, the acylation of peptides during the erosion of poly(lactic acid) and poly(lactic-co-glycolic acid) microspheres has been described in the literature. To investigate whether insulin is prone to the covalent attachment of lactic or glycolic acid, insulin-loaded PLA and PLGA microspheres containing 5% bovine insulin were manufactured using a w/o/w multiple emulsion-solvent evaporation technique. Microspheres were characterized for their insulin encapsulation efficiency and release characteristics in phosphate-buffered saline (PBS) at pH 7.4 and 37 degrees C. Moreover, the stability of the peptide during 18 days of release was evaluated using HPLC and HPLC-MS techniques. The results showed that the insulin loading efficiencies of PLA and PLGA microspheres were 75.18% and 79.63%, respectively. The microspheres were spherical with relatively porous surfaces with an average diameter of 40 and 53 mum, respectively. Insulin release from the microspheres was characterized by an initial burst, which was attributed to the amount of protein located on or close to the microsphere surface. The total ion chromatogram (TIC) of insulin samples extracted after 18 days of erosion in phosphate buffer pH 7.4 at 37 degrees C revealed that deamidation was the major mechanism of instability. Surprisingly, no acylation products were found. Control experiments in concentrated lactic acid solutions confirmed a minimal reactivity of the peptide under these conditions.

Formulation and evaluation of mefenamic acid sustained release matrix pellets.

The objective of the study was to prepare mefenamic acid (MA) sustained release matrix pellets and investigate the formulation parameters affecting pellet attributes and drug release in vitro. Amixer torque rheometer (MTR) was used to characterize the rheological properties of wet mass used in pellet formulation. Mefenamic acid pellets were prepared by extrusion/spheronization techniques using microcrystalline cellulose (MCC) in combination with lactose as pellet forming agents and water as the binding liquid. Also, the prepared pellets were characterized for their particle size and in vitro drug dissolution. The results revealed that the increase in lactose weight ratio to MCC resulted in a significant reduction of both maximum torque and binder ratios, while the addition of 2 % (m/m) polyvinyl pyrolidone (PVP) to MCC-lactose influenced only the mean torque rather than the wetting liquid (water). Particle size ranged from 945 to 1089 mm and had small span values (0.56-0.67). Furthermore, an inverse relation was observed between the rheological character of pellet wet masses (expressed by peak torque) and in vitro release rate. Increasing MAloading from 2.5 to 5 and 10 % was accompanied by a decrease in dissolution rates. In conclusion, properties of MA matrix pellets could be successfully monitored by controlling the wet mass characteristics by measuring torque.