Bashar M Altaani

Scopus Publications

Hydroxypropyl Beta Cyclodextrin as a Potential Surface Modifier for Paclitaxel Nanocrystals
Razan Haddad, Nasr Alrabadi, Bashar Altaani, Majed Masadeh, and Tonglei Li
Springer Science and Business Media LLC
Paclitaxel (PTX) is a hydrophobic chemotherapeutic agent cytotoxic against many serious cancers. This study aimed at designing novel PTX nanocrystals (PTX-NCs) coated with the biocompatible and biodegradable hydroxypropyl-beta-cyclodextrin (HPβCD) polymer with specific characteristics through the formation of a non-inclusion complex. Briefly, PTX-NCs were prepared by the anti-solvent method followed by homogenization. Then, the surface of the prepared PTX-NCs was modified using the HPβCD coat (HPβCD-PTX-NCs). The prepared nanocrystals, both coated and uncoated, were characterized in terms of size, polydispersity index, charge, morphology, and stability. Moreover, the nanocrystals were investigated using powder X-ray diffraction (PXRD), differential scanning calorimeter (DSC), and Fourier transform infrared spectroscopy (FTIR). As well, the in vitro release of PTX from the nanocrystals was determined under conditions similar to the IV route of administration. Furthermore, the tendency of the nanocrystals to induce hemolysis was investigated. Results indicated that the size was about 241.4 and 310.5 nm, the polydispersity index was 0.14 and 0.21, and the zeta potential was about − 22.6 and − 16.4 mV for PTX-NCs and HPβCD-PTX-NCs, respectively. Additionally, the PXRD, FTIR, and DSC profiles can be explained by the NCs’ integrity and coat formation. The SEM images showed that both PTX-NCs and HPβCD-PTX-NCs have rod-like structures. Moreover, HPβCD-PTX-NCs had significantly superior in vitro release than both PTX-NCs and PTX. Interestingly, the hemolytic assay showed that HPβCD-PTX-NCs had a more efficient and safer profile than PTX-NCs. This study emphasized that HPβCD could be an interesting candidate for the surface modification of PTX-NCs providing superior properties such as release and safety profiles.

Co-crystallization of Amoxicillin Trihydrate and Potassium Clavulanate Provides a Promising Approach for Preparation of Sustained-Release Microspheres
Rana Obaidat, Batool Al-Ghzawi, Bashar Al-Taani, and Nizar Al-Shar’i
Springer Science and Business Media LLC
This work aimed to prepare sustained-release microspheres for amoxicillin trihydrate and potassium clavulanate. Co-crystals of amoxicillin trihydrate and potassium clavulanate were prepared using three different techniques, including supercritical fluid technology. Full characterization was performed for the prepared co-crystals, including molecular dynamic simulation. Next, the co-crystals were microencapsulated with ethylcellulose using the emulsion solvent evaporation method in spherical microspheres. Physicochemical characterizations for the prepared co-crystal were performed using FTIR, DSC, and PXRD. Finally, scanning electron microscopy was used to assess the morphology of the prepared microspheres. Physicochemical studies showed the solid-state interaction between amoxicillin trihydrate and potassium clavulanate in the prepared co-crystals. The total energy suggested differences between the three methods of co-crystal preparations suggesting some structural changes have occurred with better stabilization at supercritical fluid technology. Encapsulation of the co-crystals was successfully performed using ethylcellulose polymer. The in vitro release studies revealed sustained-release profiles for the co-crystal microspheres. Potassium clavulanate was released at a lower rate from the crystal microspheres prepared using co-crystals than the release in microspheres of potassium clavulanate alone. The empirical Higuchi model best fitted the in vitro release profile for amoxicillin trihydrate-potassium clavulanate co-crystal microspheres.

Validation of RP-HPLC Method for Determination of Omeprazole in Dissolution Media and Application to Study in-vitro Release from SolidSNEDDS
Suhair S. Al-Nimry, Khouloud A. Alkhamis, and Bashar M. Altaani
Bentham Science Publishers Ltd.
Background: Omeprazole has poor water solubility, is unstable in acidic solutions, and undergoes first pass metabolism which results in lowering its bioavailability. A solid Self-Nano Emulsifying Drug Delivery System (SNEDDS) was previously prepared to enhance its dissolution. Objective: Development and validation of a RP-HPLC method with UV detection for the determination of omeprazole in 0.1N HCl and in 0.01 M phosphate buffer (pH 7.4). Methods: Validation was according to the ICH Q2 (R1) guidelines in terms of linearity, accuracy and precision, lower limit of quantification, sensitivity, specificity, and robustness. The developed and validated method was used to study the in-vitro dissolution of the drug from the solid-SNEDDS, commercial products and of the unprocessed drug. The dissolution was studied in 500 ml of 0.1N HCl during the first 2 hours, and 900 mL of 0.01 M phosphate buffer (pH 7.4) during the last hour (37 ± 0.5 oC and 100 rpm). Results: The method was linear in the range 1-50 μg/ml, accurate and precise as indicated by the ANOVA test. It was specific to the drug and the pharmaceutical excipients did not affect the determination of its concentration. The method was robust to small changes in pH, composition, and flow rate of the mobile phase. The dissolution rate of omeprazole from the Solid-SNEDDS was faster than that from two commercial dosage forms and than the dissolution rate of the unprocessed drug. Conclusion: The method met the acceptance criteria and was applied successfully in studying the rate of dissolution of the drug.

Paclitaxel Drug Delivery Systems: Focus on Nanocrystals’ Surface Modifications
Razan Haddad, Nasr Alrabadi, Bashar Altaani, and Tonglei Li
MDPI AG
Paclitaxel (PTX) is a chemotherapeutic agent that belongs to the taxane family and which was approved to treat various kinds of cancers including breast cancer, ovarian cancer, advanced non-small-cell lung cancer, and acquired immunodeficiency syndrome (AIDS)-related Kaposi’s sarcoma. Several delivery systems for PTX have been developed to enhance its solubility and pharmacological properties involving liposomes, nanoparticles, microparticles, micelles, cosolvent methods, and the complexation with cyclodextrins and other materials that are summarized in this article. Specifically, this review discusses deeply the developed paclitaxel nanocrystal formulations. As PTX is a hydrophobic drug with inferior water solubility properties, which are improved a lot by nanocrystal formulation. Based on that, many studies employed nano-crystallization techniques not only to improve the oral delivery of PTX, but IV, intraperitoneal (IP), and local and intertumoral delivery systems were also developed. Additionally, superior and interesting properties of PTX NCs were achieved by performing additional modifications to the NCs, such as stabilization with surfactants and coating with polymers. This review summarizes these delivery systems by shedding light on their route of administration, the methods used in the preparation and modifications, the in vitro or in vivo models used, and the advantages obtained based on the developed formulations.

Hydrolysis kinetics of the prodrug myristyl nicotinate
Bashar Altaani, Razan Haddad, Aliaa Al-Tarakji, and Nasr Alrabadi
Informa UK Limited
Abstract Myristyl nicotinate is a prodrug of nicotinic acid. In this research, the kinetics of hydrolysis for myristyl nicotinate was studied in an aqueous phosphate buffer solution within a 5–10 pH range and constant ionic strength at a high temperature which was 80 °C to perform accelerated hydrolysis experiments. The effect of temperature, ionic strength, buffer concentrations, and buffer type was studied. The degradation was monitored using a validated HPLC method. The kinetics of hydrolysis of myristyl nicotinate was also studied in skin and liver homogenates. The hydrolysis was found to follow pseudo-first-order kinetics. The rate constant was calculated from the slope of a linear plot of Ln transformation (Ln) of the remaining parent prodrug concentration versus time. The hydrolysis was found pH- dependent, and a pH rate profile was constructed. Moreover, the hydrolysis rate of the prodrug was found to be buffer species dependent. Carbonate buffer has the most catalytic effect over borate and phosphate buffers. The effect of temperature on the kinetics of hydrolysis of myristyl nicotinate in phosphate buffer at pH 9 at 343, 348, 353, and 358°K was studied. The hydrolysis was found to follow the Arrhenius equation. From the Arrhenius plot, the half-life at 25 °C, and the activation energy were calculated and were found to be 466.5 days and 24.57 kcal mol−1, respectively. The hydrolysis of the prodrug was faster in liver and skin homogenates than those in aqueous buffer solutions. The pseudo-first-order rate constants were found to be 0.012, 0.028 min−1 for myristyl nicotinate in the liver, and skin homogenates, respectively.

Jojoba oil-based microemulsion for transdermal drug delivery
ShereenMashhour Assaf, KhalidTaieb Maaroof, BasharMohammad Altaani, MowafaqMohammed Ghareeb, and AmaneAwad Abu Alhayyal
Research in Pharmaceutical Sciences Medknow
Background and purpose: Microemulsions are gaining an increased interest in transdermal drug delivery. Microemulsions are stable, easy to prepare, and provide high solubilizing capacity for various drugs. The aim of this work was to prepare microemulsions from jojoba oil for transdermal delivery of ketorolac and lidocaine HCl with improved permeation. Experimental approach: Microemulsions based on jojoba oil as the oil phase were formulated for transdermal delivery of lidocaine HCl and ketorolac. Brij 97 was selected as surfactant and hexanol as cosurfactant. Pseudoternary phase diagrams were constructed. Selected microemulsion formulations were characterized for their physical properties and in vitro drug permeation. Findings/Results: Water-in-oil microemulsions were obtained with droplet sizes not more than 220 nm. The viscosity of the microemulsions was linked to the viscosity of the surfactant used. Improved drug permeation rates were observed for both model drugs. The significant increase in permeation rate in presence of hexanol was due to its impact on skin integrity as indicated by the histopathological study. Drug permeation enhancements were caused by the surfactant, the cosurfactant used, jojoba oil itself, and the microemulsion formulation. Higher surfactant content showed lower lag times and better flux. Conclusion and implications: Jojoba oil microemulsions are considered promising vehicles for transdermal delivery of ketorolac and lidocaine HCl with improved drug permeation. Jojoba oil-based microemulsion would present a safe and effective means for delivering drugs through the skin.

Development and Evaluation of Cocoa Butter Taste Masked Ibuprofen Using Supercritical Carbon Dioxide
Rana Obaidat, Haneen Aleih, Hadeia Mashaqbeh, Bashar Altaani, Mo’tasem M. Alsmadi, and Mohammad Alnaief
Springer Science and Business Media LLC
Masking the unpleasant taste of the pharmaceutically active ingredients plays a critical role in patient acceptance, particularly for children. This work’s primary objective was the preparation of taste-masked ibuprofen microparticles using cocoa butter with the assistance of supercritical fluid technology. Microparticles were prepared by dissolving ibuprofen in melted cocoa butter at 40 °C. The solution was then introduced into a supercritical fluid unit and processed at 10 MPa CO2 pressure for 30 min. The product was collected after depressurizing the system. The effect of the drug to cocoa butter ratio and the supercritical fluid units’ configuration on product quality was evaluated and compared with the sample prepared by a conventional method. Physicochemical characterization of the prepared product, including particle size, crystallinity, entrapment efficiency, in vitro drug release, and product taste using a human volunteer panel was conducted. The produced microparticles were in the range of 1.42 to 15.28 μm. The entrapment efficiency of the formulated microparticles ranged from 66 to 81%. The drug:polymer ratio, the configuration of the supercritical fluid unit, and the method of preparation were found to have a critical role in the formulation of ibuprofen microparticles. Taste evaluation using human volunteers showed that microparticles containing 20% drug and processed with supercritical fluid technology were capable of masking the bitter taste of ibuprofen. In conclusion, the dispersion of ibuprofen in cocoa butter using supercritical fluid technology is a a promising innovative method to mask the bitter taste of ibuprofen.

Preparation and characterization of ethylcellulose microspheres for sustained-release of pregabalin
Haya Yasin, Bashar Al-Taani, and MutazSheikh Salem
Medknow
Background and purpose: Pregabalin is used in the treatment of epilepsy, chronic pain, and other psychological disorders. Preparation of pregabalin in the sustained-release formulation will enhance patient compliance and reduce the incidence of side effects. The aim of this study was to prepare sustained-release microspheres for pregabalin utilizing ethylcellulose and evaluate the processing factors that influence the fabrication and the performance of the prepared microspheres. Experimental approach: The microspheres were prepared using the water-oil-oil double emulsion solvent evaporation method. Microspheres were characterized for particle size, encapsulation efficiency, and in vitro drug release. The influence of the processing variables on the characteristics of the prepared microspheres was studied. Microspheres solid-state characterization performed using differential scanning calorimetry, Fourier transform infrared spectroscopy and scanning electron microscopy. Findings/Results: The results described in the context of the current work illustrated the suitability of the water-oil-oil system in the preparation of sustained-release microspheres for pregabalin. The optimum formulation was prepared at a drug to polymer ratio of 1:3 w/w, stirring speed of 600 rpm, surfactant concentration of 1.5%, and external phase volume of 150 mL. This formula produced microspheres particle size in the range 600-1000 μm, with 87.6% yield, and 80.14 ± 0.53% encapsulation efficiency. Drug release from the microspheres was found to be diffusion controlled, with a pH-independent behavior. Conclusion and implication The current work presented a successful attempt to fabricate a sustained-release microsphere comprising pregabalin. This will help overcome the frequent dosing problems with conventional pregabalin dosage forms and improve product performance.

The relationship between the Hammett acidity and the decomposition of cefotaxime sodium in the solid state
Bashar M. Altaani, Khouloud A. Alkhamis, Shaima’a Abu Baker, and Razan Haddad
Informa UK Limited
Abstract It was of interest to correlate the solid-state acidity to the decomposition of a model drug namely cefotaxime sodium. Amorphous samples containing either an indicator probe (thymol blue) or a model drug (cefotaxime sodium) were prepared by freeze-drying. The prepared samples were characterized using XRPD and Karl Fischer titrimetry. The acidity in the solid state was measured using reflectance spectroscopy. The kinetics of hydrolysis of cefotaxime sodium was studied in solid state at 50 °C in the Hammett acidity range of 8.12–8.61 and at constant ionic strength. The kinetics of decomposition of cefotaxime sodium in solution was also studied in basic media in the pH range of 7.9–8.9 at 50 °C and at constant ionic strength. The degradation was monitored using a validated HPLC method. The hydrolysis was found to follow pseudo-first-order kinetics in solution and solid state. The results obtained showed that there is a good correlation between the Hammett acidity function and the base-catalyzed decomposition of cefotaxime sodium in the solid state. The Hammett acidity-rate profile for cefotaxime decomposition is similar to the pH-rate profile obtained in solution. The decomposition of cefotaxime sodium in the solid state was found to be sensitive to the ionic strength.

Solid self-nanoemulsifying drug delivery system filled in enteric coated hard gelatin capsules for enhancing solubility and stability of omeprazole hydrochloride
Suhair S. Al-Nimry, Khouloud A. Alkhamis, and Bashar M. Altaani
Informa UK Limited
Abstract Omeprazole has poor water solubility, low stability in acidic solutions, and is subject to first pass metabolism resulting in low bioavailability. The objective was to enhance the dissolution and stability by preparing a solid-self nanoemulsifying drug delivery system (SNEDDS) and filling it in enteric coated HGCs. Drug solubility in many oils, surfactants, and cosurfactants was studied. Different SNEDDS were prepared and ternary phase diagrams were constructed. The optimum SNEDDS was evaluated. It was converted into solid by adsorption onto Neusilin® US2, and evaluated. Emulsions formed using Capryol 90, Cremophor RH 40, and ethanol formed spontaneously and were clear. Droplet size was 19.11 ± 3.11 nm, PDI was 0.18 ± 0.05, and zeta potential was –3.9 ± 1.56 mV. Non-medicated SNEDDS was thermodynamically stable. Cloud point was 88 ± 2 °C. Encapsulation efficiency and drug loading of solid-SNEDDS were 98.56 ± 0.44 and 1.29 ± 0.01%, respectively. Flow properties were much enhanced. Crystalline drug was adsorbed/precipitated onto Neusilin® US2 in amorphous form. Dissolution rate was enhanced as compared to commercial products and unprocessed drug. The drug was unstable at the accelerated stability conditions. Accordingly, the traditional stability study at 25 °C should be conducted. In conclusion, the solid-SNEDDS filled in enteric coated HGCs enhanced the dissolution rate and stability in acidic pH.

Enhancement of dissolution of atorvastatin through preparation of polymeric solid dispersions using supercritical fluid technology
Bashar Altaani, Rana Obaidat, and Walaa Malkawi
Medknow
Background and purpose: This study aimed at preparation of solid dispersions in order to enhance dissolution of poorly water-soluble atorvastatin using supercritical CO2 technology. Atorvastatin has poor bioavailability of 12%, mainly due to poor water solubility and dissolution. Dispersion of drugs in various hydrophilic carriers using supercritical fluid technology has been found to be an outstanding method to prepare solid dispersion. Experimental approach: Four different polymers were employed. These were polyvinyl pyrrolidone K30 (PVP), polyethylene glycol 6000 (PEG), Soluplus® and chitosan. Full physicochemical characterizations were performed in addition to in vitro dissolution study. Findings / Results: The used polymers enhanced the dissolution rate of atorvastatin. However, supercritical parameters affected the dissolution profile and drug loading efficiency of the prepared dispersions. High performance liquid chromatography assay indicated the stability of the prepared PEG, Soluplus® andchitosan-based dispersions. On the other hand, PVP solid dispersions were not stable and formed sticky paste. Powder X-ray diffraction showed similar patterns for PEG-based dispersions after exposure to storage condition, while the intensity of atorvastatin peaks increased after three months of storage of Soluplus® and chitosan dispersions. Conclusion and implications: Supercritical fluid technology proved to have great potential to prepare dispersions for biopharmaceutics classification system (BCS) class II drugs. Dissolution enhancement of atorvastatin was achieved through successful preparation of polymeric dispersions of the drug using the supercritical technology without further addition of solvents.

Oral Delivery of Teriparatide Using a Nanoemulsion System: Design, in Vitro and in Vivo Evaluation
Bashar M Altaani, Ammar M Almaaytah, Suha Dadou, Khouloud Alkhamis, Mousa H Daradka, and Wael Hananeh
Springer Science and Business Media LLC

Vitamin d pretreatment attenuates ciprofloxacin-induced antibacterial activity
Majed M Masadeh, Karem H Alzoubi, Bashar M Al-Taani, Majd M Masadeh, Zainah O Aburashed, and Nasr Alrabadi
Informa UK Limited
Background Ciprofloxacin is an antimicrobial that is commonly used to treat several types of infections. It exerts its antimicrobial activity through interfering with bacterial DNA replication and transcription, leading to increase oxidative stress and eventually bacterial death. Vitamin D, on the other hand, has been found to have DNA protective and antioxidant effects. In the current study, the possible interactive effect of vitamin D on ciprofloxacin-induced cytotoxicity was investigated in various standard bacterial strains. Methods The bacterial strains that were used include Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Staphylococcus epidermidis, Acinetobacter baumannii, Proteus mirabilis, and Klebsiella pneumoniae. The antibacterial effect of ciprofloxacin with and without vitamin D treatment of the bacteria was assessed using disc diffusion method and by measuring the minimum inhibitory concentration (MIC) and zones of inhibition of bacterial growth. Moreover, reactive oxygen species (ROS) generation after pretreatment of E. Coli cells with ciprofloxacin and/or vitamin D was measured as a function of as a function of hydrogen peroxide generation. Results Ciprofloxacin demonstrated a potent antibacterial effect against the tested strains of bacteria. Moreover, pretreatment with vitamin D resulted in protecting the bacteria from the cytotoxicity of ciprofloxacin, this was indicated by the significantly smaller zones of inhibition and higher MIC values compared to ciprofloxacin alone as well as reduced ciprofloxacin-induced ROS generation after treatment with vitamin D. Conclusion Results revealed the possible reduction in the activity of ciprofloxacin when used in combination with vitamin D. This could be explained by the ability of vitamin D to reduce oxidative stress in the bacterial cells.

Enhancement of dissolution and stability of candesartan cilexetil–loaded silica polymers
Mai Khanfar, Bashar Al Taani, and Eman Mohammad
Innovare Academic Sciences Pvt Ltd
Objective: To prepare stable amorphous solid dispersions of candesartan cilexetil (CAN) with different types of silica, including non-porous (aerosil 200) and porous silica (sylysia 350) using the spray-drying method. Methods: various ratios of candesartan cilexetil (CAN) were spray dried with aerosil and sylysia. Powder x-ray diffraction (x-ray) differential scanning calorimetry (DSC), SEM were used to characterize the spray dried powders in addition to dissolution and stability studies. Results: X-ray results showed that the spray–dried (CAN) in the prepared solid dispersion were in amorphous form irrespective of the used silica. In (DSC) analysis, the melting peak of spray-dried (CAN-silica) solid dispersion disappeared. Dissolution property of (CAN) was remarkably improved by formulating with silica particles. In comparing the effect of the type of the silica particles, the dissolution rate of (CAN) from the spray-dried (CAN-sylysia) was faster than that (CAN-aerosil 200) irrespective of the drug content. It was also shown that the spray-dried formulation with silica did not recrystallize when storing at severe storage conditions (40 °C, 75% RH) for three months, while spray-dried (CAN) without silica easily re-crystallized under the same conditions. Conclusion: Spray drying of (CAN) with sylysia 350 is an efficient method to enhance the dissolution and stability of the drug.

Preparation and Characterization of an Oral Norethindrone Sustained Release/Controlled Release Nanoparticles Formulation Based on Chitosan
Bashar M. Altaani, Suhair S. Al-Nimry, Razan H. Haddad, and Rana Abu-Dahab
Springer Science and Business Media LLC
Norethindrone has short half-life and low bioavailability. The objective was to prepare an oral Sustained Release/Controlled Release (SR/CR) Liquid Medicated Formulation (LMF) to enhance bioavailability and improve patient compliance. Norethindrone was solubilized in HP-β-CD then complexed with different concentrations of Low Molecular Weight Chitosan (LMWC) (mucoadhesive). PolyElectrolyte Complexes (PECs) were homogenized with oleic acid using different concentrations of tween 80 to form LMFs (nanoemulsions). PECs and LMFs were characterized using different techniques. LMF 2 (optimum formula containing 2.5% w/v LMWC 11 kDa) was administered orally to dogs and mice for pharmacokinetic and adhesion evaluation. DSC, FTIR spectroscopy and SEM images indicated complex formation. Mean diameters of PECs were 183–425 nm, mean zeta potentials were + 18.6–+ 31 mV, and complexation efficiencies were 18.0–20.6%. Ten to fifteen percent tween was needed to prepare homogenous LMFs. Mean diameter of LMF 2 was 10.5 ± 0.57 nm, mean zeta potential was − 11.07 ± − 0.49 mV, encapsulation efficiency was 95.28 ± 1.75%, and each mL contained 145.5 μg norethindrone. SEM images showed spherical homogeneous oil droplets. All of these parameters were affected by molecular weight and concentration of chitosan. Norethindrone release from LMFs was controlled (zero order) for 96 h. It was little affected by molecular weight and concentration of chitosan but affected by concentration of tween 80. LMF 2 adhered to GIT for 48 h and enhanced the bioavailability. It showed no cytotoxicity after considering dilution in GIT and was stable for 3 months refrigerated. In conclusion an effective SR/CR LMF was prepared.

RP-HPLC method for determination of norethindrone in dissolution media and application to study release from a controlled release nanoparticulate liquid medicated formulation
Journal of Applied Pharmaceutical Science
Several methods are available for the determination of norethindrone. These methods are either complicated or need validation. The objective of this work was to develop and validate a simple reversed phase-high performance liquid chromatographic method for the determination of norethindrone in dissolution media. A Thermo Scientific C18 column (250 mm × 4.6 mm ID, 5 μm pore size) was used. A mobile phase consisting of deionized water: acetonitrile (50:50, v/v) and 5 ml/l acetic acid was used. The flow rate was 1.3 ml/minute and the wavelength of the detection was 245 nm. Validation of linearity, accuracy and precision, limit of detection, limit of quantification, specificity, and stability (degradation) was carried out according to the International Conference on Harmonization guidelines. The developed and validated method was used to study norethindrone release from a nanoparticulate liquid medicated formulation (LMF). The results indicated that the method was simple, accurate and precise, and met the acceptance criteria. The drug exhibited higher stability in basic media when compared to acidic media. Drug release from a LMF (nanoemulsion) followed zero order kinetics. In conclusion, a simple method was developed, validated, and used successfully in evaluating in vitro drug release from a sustained release/controlled release nanoparticulate LMF.

Depolymerization of HMW into a predicted LMW chitosan and determination of the degree of deacetylation to guarantee its quality for research use

Enhancement of the release of curcumin by the freeze drying technique using inulin and neusilin as carriers
Bashar Al-Taani, Mai Khanfar, and Osama Abu Alsoud
Innovare Academic Sciences Pvt Ltd
Objective: Curcumin (CUR), the active ingredient in turmeric has been proven to possess many therapeutic activities chiefly as anti-inflammatory and antioxidant. Unfortunately, CUR suffers from low bioavailability and dissolution due to its poor water solubility. The aim of this work was to enhance the dissolution of CUR by converting it into an amorphous form by freeze-drying and using different carriers. Methods: Different solid dispersions of CUR with Inulin and Neusilin US2 at different ratios using the freeze-drying technique were prepared. The various prepared formulas were characterized using differential scanning calorimetry, X-ray diffraction studies, fourier transform infrared and scanning electron microscopy. Release studies, as well as stability studies of CUR from different formulas, were done. Results: Formulation containing CUR, Inulin and Neusilin US2 at a ratio of 1:5:1 showed the highest CUR release during dissolution testing. The percent CUR release was 98% in comparison with that of 2% from the reference raw material. Physical stability testing showed that CUR remained in the amorphous state for 3 mo. Conclusion: Inulin and Neusilin US2 combinations were found to be effective in enhancing the solubility and dissolution rate of CUR, and stabilizing the amorphous form in the prepared solid dispersion.

Enhancement of the dissolution and bioavailability from freeze-dried powder of a hypocholesterolemic drug in the presence of Soluplus
Mai Khanfar, Bashar Al-Taani, Motasem Alsmadi, and Aref Zayed
Elsevier BV

Low molecular weight chitosan-coated PLGA nanoparticles for pulmonary delivery of tobramycin for cystic fibrosis
Nusaiba Al-Nemrawi, Nid’’A Alshraiedeh, Aref Zayed, and Bashar Altaani
MDPI AG
(1) Background: Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) loaded with Tobramycin were prepared using a solvent-evaporation method. (2) Methods: The NPs were coated with low molecular weight chitosan (LMWC) to enhance the mucoadhesiveness of PLGA-NPs. The following w/w ratios of tobramycin to LMWC were prepared: control (0:0.50), F0 (1:0.25), F0.5 (1:0.5), and F1 (1:1). (3) Results: The results showed that the size of the particles increased from 220.7 nm to 575.77 nm as the concentration of LMWC used in the formulation increased. The surface charge was also affected by the amount of LMWC, where uncoated-PLGA nanoparticles had negative charges (−2.8 mV), while coated-PLGA NPs had positive charges (+33.47 to +50.13 mV). SEM confirmed the size and the spherical homogeneous morphology of the NPs. Coating the NPs with LMWC enhanced the mucoadhesive properties of the NPs and sustained the tobramycin release over two days. Finally, all NPs had antimicrobial activity that increased as the amount of LMWC increased. (4) Conclusion: In conclusion, the formulation of mucoadhesive, controlled-release, tobramycin-LMWC-PLGA nanoparticles for the treatment of P. aeruginosa in cystic fibrosis patients is possible, and their properties could be controlled by controlling the concentration of LMWC.

Delivery of peptidic gonadotropin releasing hormone antagonists
Rawda Y. AlSheyyab, Bashar M. Al-Taani, Rana M. Obeidat, Motasem M. Alsmadi, Rafeef K. Masaedeh, and Raghda N. Sabat
Bentham Science Publishers Ltd.
GnRH antagonists have several clinical applications in prostate cancer, regulation of ovulation induction in females, breast cancer, male contraception and others. Antagonists differ from natural GnRH decapeptide in having five or more amino acid substitutions, whereas most of the antagonists are available as subcutaneous (SC) formula for injection some are formulated as a depot formulation for sustained release (e.g., Cetrorelix, Degarelix). Systemic delivery of cetrorelix acetate by intratracheal route can be achieved using dry powder for inhalation of the adhesive mixture when the powder deposition reaches stage four. The oral route for systemic delivery of peptide without its degradation can be achieved using gastrointestinal permeation enhancement technology GIPET® provided by acyline.

Effect of different polymeric dispersions on In-vitro dissolution rate and stability of celecoxib class II drug
Rana M. Obaidat, Bashar AlTaani, and Anoud Ailabouni
Springer Science and Business Media LLC

A new controlled-release liquid delivery system based on diclofenac potassium and low molecular weight chitosan complex solubilized in polysorbates
N. A. Athamneh, B. M. Tashtoush, A. M. Qandil, B. M. Al-Tanni, A. A. Obaidat, N. D. Al-Jbour, N. A. Qinna, K. Al-Sou’od, M. M. Al-Remawi, and A. A. Badwan
Informa UK Limited
A complex of low molecular weight chitosan (LMWC) with oleic acid and diclofenac potassium (DP) was prepared and dispersed in high concentrations of polysorbate 20, 60 and 80 in water to form a solution which releases its components slowly. The formed complex was characterized using different analytical methods. The size of the resulted nanoparticles and the effect of tweens on size were followed using dynamic light scattering (DLS). The release of DP from this delivery system was monitored by altering the molecular weight of chitosan and the type and concentration of the polysorbates used. The most suitable preparation consisted of DP, LMWC 13 kDa, and oleic acid. This was dispersed in 5% Tween 80 and the release was followed by the adaptation of USP II apparatus using a cellophane bag. This preparation offers a release of up to 24 h.

Preparation and characterization of microemulsion formulations of nicotinic acid and its prodrugs for transdermal delivery
Bassam M. Tashtoush, Amina N. Bennamani, and Bashar M. AL-Taani
Informa UK Limited
At pharmacological doses, nicotinic acid has a lipid-regulating effect and is in use clinically for that purpose. However, despite of all features, its utility is strongly limited by several disadvantages such as, extensive hepatic metabolism and flushing. Transdermal delivery of nicotinic acid may, therefore, be the solution to reducing side effects associated with oral administration, and to maintaining constant therapeutic blood levels for longer duration. The aim of this investigation was to develop a suitable formulation or select a suitable vehicle for the transdermal delivery of highly lipophilic prodrugs of nicotinic acid (dodecyl and myristyl nicotinate) designed to deliver nicotinic acid through skin without causing vasodilatation and flushing and optimizing its delivery to the blood stream. A microemulsion system and penetration enhancers have been attempted in this study. The microemulsion system was composed of isopropyl myristate (IPM), water and a 4:1 (w/w) mixture of Labrasol and Peceol where a pseudoternary phase diagram was constructed. Furthermore, the microemulsion formulations with different component ratios were characterized by determination of conductivity, pH, particle size, viscosity and refractive index. According to the particle size analysis, conductivity and viscosity measurements, the microemulsion formulations that formed were of oil-in-water type. The transdermal permeability of nicotinic acid and its prodrugs was evaluated in vitro using Franz diffusion cells fitted with mice skin and nicotinic acid concentration was analyzed by high performance liquid chromatography. A theoretical design of percutaneous penetration optimization in which prodrugs derivation and enhancer application are combined based on the skin diffusion model was experimentally verified. The selected formulations seemed promising for developing a transdermal drug delivery system of nicotinic acid from dodecyl nicotinate that would offer advantages like possible controlled drug release, reduced flushing, increased drug stability and ease of large-scale production.

Release behaviour of diclofenac sodium dispersed in Gelucire® and encapsulated with alginate beads
Bashar Al-Taani, Mai S. Khanfar, Mutaz Sheikh Salem, and Alsayed Sallam
Informa UK Limited
Sustained release polymeric particles containing diclofenac sodium dispersed in Gelucire® matrix and encapsulated in calcium alginate shell were prepared with different drug-to-polymer ratios and also with different concentrations of sodium alginate for a fixed drug-to-polymer ratio in an aqueous environment. Spherical particles were formed by dropping an emulsion of diclofenac sodium in Gelucire® matrix, emulsified with sodium alginate, into calcium chloride solution. The gelled beads formed by ionotropic gelation of alginate with calcium ions showed sustained release of the water soluble drug in in-vitro release study. Drug release was a function of square-root of time, suggesting a matrix diffusion release pattern. The rate of release was significantly suppressed with increasing proportions of Gelucire® in the mixture. Sustained and complete release was achieved with Gelucire® of low melting point and low HLB value. No significant drug release occurred in a dissolution medium of pH 1.5, whereas complete release was observed at pH 6.8, consistent with considerable swelling of the alginate gel at this pH.

Bashar M Altaani

EDUCATION

RESEARCH, TEACHING, or OTHER INTERESTS

Scopus Publications

RECENT SCHOLAR PUBLICATIONS