Co-spray Drying Drugs with Aqueous Polymer Dispersions (APDs)-a Systematic Review
Authors : Nizar Al-Zoubi , Ioannis Partheniadis , Ahmad Aljaberi , Ioannis Nikolakakis
Abstract : Aqueous colloidal dispersions of water-insoluble polymers (APDs) avoid hassles associated with the use of organic solvents and offer processing advantages related to their low viscosity and short processing times. Therefore, they became the main vehicle for pharmaceutical coating of tablets and multiparticulates, a process commonly employed using pan and fluidized-bed machinery. Another interesting although less common processing approach is co-spray drying APDs with drugs in aqueous systems. It enables the manufacture of capsule- and matrix-type microspheres with controllable size and improved processing characteristics in a single step. These microspheres can be further formulated into different dosage forms. This systematic review is based on published research articles and aims to highlight the applicability and opportunities of co-spray drying drugs with APDs in drug delivery.
Keywords : agglomerates; aqueous polymer dispersions; biological drugs; modified release; spray drying; taste masking.
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siRNA as a Potential Therapy for COVID-19
Authors : Ahmad Aljaberi , Eman M Migdadi , Khalid M Abu Khadra , Mahmoud Abu Samak , Iman A Basheti , Nizar Al-Zoubi
Abstract : Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) is a highly contagious virus causing COVID-19 disease that severely impacted the world health, education, and economy systems in 2020. The numbers of infection cases and reported deaths are still increasing with no specific treatment identified yet to halt this pandemic. Currently, several proposed treatments are under preclinical and clinical investigations now, alongside the race to vaccinate as many individuals as possible. The genome of SARS-CoV2 shares a similar gene organization as other viruses in the Coronaviridae family. It is a positive-sense, single-stranded RNA. This feature suggests that RNA interference (RNAi) is an attractive prophylactic and therapeutic option for the control of this pandemic and other possible future pandemics of the corona viruses. RNAi utilizes the use of siRNA molecules, which are 21-29 nt duplexes RNA molecules that intervene with targeted gene expression in the cytoplasm by a specific mechanism of complementary destruction of mRNA. Previous experience with SARS-CoV and the Middle East respiratory syndrome (MERS) showed that siRNA molecules were effective against these viruses in vitro and in vivo. Moreover, there have been extensive advances in siRNA technology in the past decade from chemistry and target selection considerations; which concluded with the successful approval of two commercial products based on siRNA technology. In addition, the current knowledge of the genome structure and functionality of the corona viruses enables the recognition of conserved sequences to optimize siRNA targeting and avoid viral escape through mutations, either for the current SARS-CoV2 as well as future corona viruses.
Keywords : COVID-19; Corona viruses; RNA interference; SARS-CoV2; respiratory syndrome; siRNA.
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The combination of omega-3 fatty acids with high doses of vitamin D3 elevate A1c levels: A randomized Clinical Trial in people with vitamin D deficiency
Authors : Abeer Barham , Beisan Mohammad , Luai Hasoun , Shady Awwad , Ibrahim Mosleh , Ahmad Aljaberi , Mahmoud Abu-Samak
Abstract : Purpose: This randomised clinical trial (RCT) was created to assess the influence of 1,25-dihydroxyvitamin D (VD3 ), omega-3 fatty acids (n-3FA) and their combination (D+) on glycated haemoglobin (A1c) levels in Jordanian peoples with vitamin D deficiency (VDD). Participants and methods: This RCT was designed to examine the follow-up (2 months) effect of either 50 000 IU VD3 , 300 mg n-3FA, or the combination of the two supplements on glycated Haemoglobin (A1c) levels in 146 Jordanian women and men with VDD, aged from 25 to 55 years. The eligible participants were randomised into four groups: Control (C); VD3 supplementation (50 000 IU of VD3 was taken weekly) (D3 ); n-3FA supplementation (300 mg of omega-3FA was taken daily) (n-3FA); VD3 and omega-3 supplementation group (D+) with the same protocol as the previous two groups. Results: The combination therapy (n-3FA plus VD3) for 8 weeks significantly increased A1c levels (5.79 ± 0.34 vs 5.41 ± 0.33, P < .001). Tukey test for post hoc comparisons of A1c at follow-up showed that the A1c mean levels were remarkably higher in the D+ study group comparing to the control group (5.78 vs 5.38). Conclusion: The intervention of n-3FA alone or in combination with high doses of VD3 may lead to negative effects on glycaemic control or accelerate the insulin resistance's development in susceptible people for diabetes mellitus (type 2).
Keywords : Vitamin D, VDD. Omega-3. A1c, diabetes
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The supplementary effects of omega-3 fatty acid alone and in a combination with vitamin D3 on serum leptin levels: A randomized clinical trial on men and women with vitamin D deficiency
Authors : Mahmoud S. Abu-Samak, Luai Z. Hasoun, Abeer Barham, Beisan A. Mohammad, Ibrahim Mosleh, Ahmad Aljaberi, Shady H. Awwad
Abstract : Purpose: This randomized clinical trial (RCT) was designed to assess the effect of VD3, n-3FA, and their combination on serum leptin levels in people with vitamin D deficiency (VDD). Subjects and methods: One hundred and forty six participants, were randomly assigned into four groups supplemented with the dose of 50,000 IU VD3 taken weekly (D), 300 mg n-3FA taken daily (Om), and their combination (D+Om) or control (C) for eight weeks. Fasting baseline and follow-up (10 weeks; 8 weeks supplementation plus washout period of 2 weeks) of serum 25 hydroxyvitamin D (25OHD), leptin, glucose, triglycerides (TG), parathyroid hormone (PTH), calcium, and phosphorus were assayed. A paired T-test was used to assess the changes in serum leptin levels over of the follow-up period. Results: Significant increase in follow-up serum leptin (10.62 ± 7.18 to 14.42 ± 8.29 ng/mL, P = 0.002) and TG (154 ± 84.4 to 200.1 ± 79, P = 0.015) levels were observed in n-3-FA supplemented group. Combination therapy (VD3 plus n-3 FA) significantly increased serum 25OHD (13.49 ± 4.64 to 37.09 ± 11.13 ng/mL, P < 0.001), TG levels (114.3 ± 57.3 to 139.1 ± 60.7 mg/mL, P = 0.007) and insignificantly serum leptin (6.74 ± 4.87 to 8.01 ± 6.77 ng/mL, P = 0.269). Conclusion: Our study referred that notable elevation in leptin and TG levels might be linked to leptin resistance. However, further RCTs are required to clarify possible consequences resulted from the extensive administration of n-3FA supplements and their combinations with high doses of VD3 supplements on humans’ health.
Keywords : leptin, n-3FA, omega, vitamin D3, diabetes
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Spray Drying for Direct Compression of Pharmaceuticals
Authors : Nizar Al-Zoubi, Shadi Gharaibeh, Ahmad Aljaberi, Ioannis Nikolakakis
Abstract : Tableting by direct compression (DC) is one of the simplest and most cost-effective drug manufacturing approaches. However, most active pharmaceutical ingredients (APIs) and excipients lack the compression and flow properties required to meet the needs of high-speed industrial tablet presses. Therefore, the majority of DC APIs and excipients are modified via processing/co-processing particle engineering techniques to boost their properties. Spray drying is one of the most commonly employed techniques to prepare DC grades of APIs and excipients with prominent advantages. This review aims to present an overview of the commercially marketed and investigationally-prepared DC APIs and excipients produced by spray drying.
Keywords : spray drying; direct compression; tablets; co-processing; multifunctional; sustained release; oral disintegration; active pharmaceutical ingredient; excipient
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Impact of the manufacturing technique on the dissolution-enhancement functionality of PEG4000 in Cilostazol tablets
Authors : Obada Sawafta, Sonia Alhadid, Izz Aldeen Abu Awwad, Eman Migdadi, Ahmad Aljaberi
Abstract : Cilostazol was selected as poorly-soluble model drug to investigate the impact of the manufacturing method on the excipient functionality of PEG4000 at various levels. Powder blends were prepared by direct compression (DC), wet granulation (WG) and hot-melt extrusion (HME). Characteristics of these blends and their compressed tablets were investigated by standard techniques. Solid-state characterization was carried out using differential scanning calorimetry (DSC). While DC trials were found with no significant differences, WG and HME showed contrasting enhancement and retardation effects regarding the dissolution profile of Cilostazol tablets depending on the level of PEG4000 incorporated. The optimal enhancement of dissolution was obtained at 10% w/w PEG4000 for tablets prepared by HME. DSC analysis indicated that no solid solutions were formed at such low levels of PEG-4000 during processing by either manufacturing techniques. Consequently, the wetting functionality and dissolution enhancement of PEG4000 was revealed to be level- and manufacturing method dependent.
Keywords : Hot-melt extrusion, Cilostazol, PEG4000, Dissolution; excipient functionality
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Hot melt extruded zein for controlled delivery of diclofenac sodium: Effect of drug loading and medium composition
Authors : Lorina Bisharat, Hatim S. Alkhatib, Amer Abdelhafez, Aya Barqawi, Ahmad Aljaberi, Sheng Qi, Alberto Berardi
Abstract : This study evaluates the potential use of zein as an excipient in hot-melt extrusion for controlled delivery of diclofenac sodium (DS). Mixtures of zein, polyethylene glycol and drug were hot melt extruded and cut into 2 mm extrudates. Extrudates were characterised using differential scanning calorimetry, X-ray powder diffraction and scanning electron microscopy. The drug in the extrudates was found to be in the non-crystalline state, independent of the drug loading. Moreover, the drug release from extrudates was investigated. The release was directly dependent on the drug loading: a controlled and nearly zero-order release was obtained at the lowest drug loading (12.5% w/w), whereas almost immediate release was achieved at higher drug loadings, i.e. 25% and 37.5%. The release was inversely dependent on the ionic strength of the medium. The influence of digestive enzymes on drug release was also studied. Pancreatin, but not pepsin, was found to have a significant influence on the drug release as well as on the microstructure of zein extrudates. These data therefore support the potential use of zein as excipient in hot melt extrusion for controlled release purposes.
Keywords : Zein; Hot melt extrusion; Controlled release; Solid dispersion; Amorphous; Diclofenac sodium
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The use of design of experiments to develop hot melt extrudates for extended release of diclofenac sodium
Authors : Mohammed Rohi Sanoufi, Ahmad Aljaberi, Iman Hamdan , Nizar Al-Zoubi
Abstract : The effect of formulation and processing parameters on processability and release from hot-melt extrusion (HME)-based matrices appears to be API and polymer dependent. Accordingly, the aim of this work was to design an extended-release formulation of diclofenac sodium by using HME technique and design of experiment (DoE). The extrudates were prepared using a vertical lab-scale single screw extruder. A D-optimal design with 16 formulations was employed to evaluate and model the effect of diclofenac sodium, ethyl cellulose and Natrosol L levels on the release profile. The percentage of drug release at 2, 4, 8 and 16 h were the dependent variables. The formulation factors that affect drug release were identified and satisfactorily modeled. The goodness of fit (R2) and goodness of prediction (Q2) parameters obtained for release responses were 0.913 and 0.682 at 2 h, 0.946 and 0.67 at 4 h, 0.942 and 0.658 at 8 h, and 0.892 and 0.673 at 16 h, respectively. The design space of optimal fractions of ethyl cellulose and Natrosol L at various drug levels was successfully constructed by response surface methodology. In conclusion, the DoE approach helped to identify and quantify formulation variables that affect the release of diclofenac sodium from HME-based formulation.
Keywords : Hot-melt extrusion; design of experiments; diclofenac sodium; ethyl cellulose; extended-release; hydroxyethyl cellulose.
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Evaluation of Spironolactone Solid Dispersions Prepared by Co-Spray Drying With Soluplus ® and Polyvinylpyrrolidone and Influence of Tableting on Drug Release
Authors : Nizar Al-Zoubi , Faten Odah , Wasfy Obeidat , Ahmad Aljaberi , Ioannis Partheniadis , Ioannis Nikolakakis
Abstract : Solid dispersions of spironolactone with Soluplus® and polyvinylpyrrolidone were prepared by spray drying according to a mixture experimental design and evaluated for moisture content, particle size, drug solubility, crystallinity (powder X-ray diffraction and differential scanning calorimetry), and physicochemical interactions (Fourier-transform infrared spectroscopy, Raman). In vitro dissolution was evaluated for the spray dried product itself and after compression into tablets, and prediction models were derived using multiple linear regression analysis. The spray dried products consisted of amorphous drug, indicated by the absence of crystalline powder X-ray diffraction peaks. Amorphization and interactions impacted changes in the Fourier-transform infrared spectroscopy spectra in the ranges 2900-3000 cm-1 (C-H) and 1600-1800 cm-1 (C=O) and caused merging at 1690 cm-1 (C=O of lactone) and 1670 cm-1 (C=O of thioacetyl group). In the Raman spectra, amorphization and interactions resulted in disappearance of peak at 1690 cm-1 (C=O) and merging of peaks at 582 and 600 cm-1 (C-S). Hydrogen bonding between the thioacetyl group of the drug with the hydroxyl groups of Soluplus® caused marked suppression of the peak at 1190 cm-1 (R-C(=O)-S vibration). Amorphization and interactions resulted in improved solubility and dissolution which was greatest for drug/Soluplus® ratio 1:4 and was also demonstrated in the corresponding tablets.
Keywords : X-ray diffractometry; amorphicity; dissolution; solid dispersion; solubility; spray drying; thermal analysis; vibration spectroscopy.
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Novel Salted Anionic-Cationic Polymethacrylate Polymer Blends for Sustained Release of Acidic and Basic Drugs
Authors : Wasfy M Obeidat , Duaa Qasim, Ali Nokhodchi, Ahmad Aljaberi, Al-Sayed Sallam
Abstract : Background: Since a unique matrix tablet formulation that independently controls the release of various drug types is in a great demand, the objective of this research was to develop a sustained release matrix tablet as a universal dosage form using a binary mixture of the salt forms of Eudragit polymers rather than their interpolyelectrolyte complexes. Methods: Tablets were prepared by wet granulation and compressed at different compression forces, depending on drug type. Dissolution tests were conducted using USP XXII rotating paddle apparatus at 50 rpm at 37°C in consecutive pH stages. Results: Tablets containing Ibuprofen (IB) as a model acidic drug and Metronidazole (MD) as a model basic drug showed controlled/sustained release behavior. For IB tablets containing 80% Ibuprofen and 5% (w/w) polymeric combination; the time for 50% of the drug release was about 24 hours compared to 8.5 hours for plain tablets containing 80% IB. In case of MD, the drug release extended to about 7 hours for tablets containing 80% MD and 5% (w/w) polymeric combination, compared to about 1 hour for plain tablets containing 80% MD. In terms of extending the release of medications, the dissolution profiles of the tablets containing polymeric salts forms were found to be statistically superior to tablets prepared by direct compression of the polymers in their powdered base forms, and superior to tablets containing the same polymers granulated using isopropyl alcohol. Conclusion: The findings indicated the significance of combining the polymers in their salt forms in controlling the release of various drug types from matrices.
Keywords : Controlled/Sustained-Release; Metronidazole; granules; ibuprofen; pH profile; polymethacrylates.
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Physicochemical and biological characterization of 1,2-dialkoylamidopropane-based lipoplexes for gene delivery
Authors : Ahmad Aljaberi , Suhair Saleh , Khalid M Abu Khadra , Molinda Kearns , Michalakis Savva
Abstract : Elucidation of the molecular and formulation requirements for efficient lipofection is a prerequisite to enhance the biological activity of cationic lipid-mediated gene delivery systems. To this end, the in vitro lipofection activity of the ionizable asymmetric 1,2-dialkoylamidopropane-based derivatives bearing a single primary amine group as the cationic head group was evaluated. The electrostatic interactions of these cationic lipids with plasmid DNA in serum-free medium were investigated by means of gel electrophoresis retardation and Eth-Br quenching assays. The effect of the inclusion of the helper lipid DOPE in the formulation on these interactions was also considered. The physicochemical properties of these lipids in terms of bilayer fluidity and extent of ionization were investigated using fluorescence anisotropy and surface potential techniques, respectively. The results showed that only the active lipid, 1,2lmp[5], existed in a liquid crystalline state at physiological temperature. Moreover, the extent of ionization of this lipid in assemblies was significantly higher that it's saturated analogues. Inclusion of the helper lipid DOPE improved the encapsulation and association between 1,2lmp[5] and plasmid DNA, which was reflected by the significant boost of lipofection activity of the 1,2lmp[5]/DOPE formulation as compared to the lipid alone. In conclusion, membrane fluidity and sufficient protonation of ionizable cationic lipid are required for efficient association and encapsulation of plasmid DNA and elicit of improved in vitro lipofection activity.
Keywords : Cationic lipids; Fluorescence anisotropy; Gene delivery; Lipofection; Membrane fluidity; Surface potential.
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Evaluation of selected biochemical parameters in the saliva of young males using mobile phones
Authors : Khalid M Abu Khadra, Ahmad M Khalil, Mahmoud Abu Samak, Ahmad Aljaberi
Abstract : The biochemical status in the saliva of 12 males before/after using mobile phone has been evaluated. Radio frequency signals of 1800 MHz (continuous wave transmission, 217 Hz modulate and Global System for Mobile Communications [GSM - non-DTX]) with 1.09 w/kg specific absorption rate (SAR) value were used for 15 and 30 min. Cell phone radiation induced a significant increase of superoxide dismutase (SOD); there was a statistically significant effect of talking time on the levels of SOD, F(2, 33) = 8.084, p < 0.05, ω = 0.53. The trend analysis suggests a significant quadratic trend, F(1, 33) = 4.891, p < 0.05; indicating that after 15 min of talking the levels of SOD increased, but as talking time increased the SOD activity started to drop. In contrast to this, there was no statistically significant effect of talking time on the level of salivary albumin, cytochrome c, catalase or uric acid. Results suggest that exposure to electromagnetic radiation may exert an oxidative stress on human cells as evidenced by the increase in the concentration of the superoxide radical anion released in the saliva of cell phone users.
Keywords : Human saliva; mobile phone; oxidative stress; radio frequency radiation; superoxide dismutase.
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Antioxidant Profile of Saliva among Young Men Using Mobile Phones
Authors : Khalid Abu Khadra, Ahmad Mohammad Khalil, Mahmoud Abu-Samak, Ahmad Aljaberi
Abstract : Oxidative stress has been implicated as a mechanism of potential health effects that may result from exposure to Radio Frequency Electromagnetic radiation (RF-EMR). A cross sectional study was designed to investigate and analyze the biochemical effects of RF-EMR emitted from mobile phones at 835 MHz and 1900 MHz bands on some biochemical markers: Superoxide dismutase (SOD), albumin, amylase, uric acid and cytochrome C in the saliva of young men (18-37 years; average age 27.74 ± 8.08). EMF caused a significant increase in the activity of SOD but a significant decrease in that of amylase in the saliva of people after using mobile phones. The increases in the activity of cytochrome C and the concentrations of albumin and uric acid were not significant. A true correlation between the salivary antioxidant biomarkers and the number of calling min., rather than the number of calls, was found. These oxidative changes may result in metabolic changes in the living cells up to oncogenic transformation. Thus, based on these findings, it is recommended that a long-term/or excessive use of mobile phones, especially by young individuals, should be avoided. This goal can be accomplished by telehealth technology promotion activities targeting the more sensitive ages, children and adolescents, since their developing brains absorb more EMR from a mobile phone. Such activities include: group discussions, public presentations and mass communication through available electronic and print media sources.
Keywords : Antioxidants; Human saliva; Mobile phone; Oxidative stress
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Assessment of oxidant/antioxidant status in saliva of cell phone users
Authors : Ahmad M Khalil, Khalid M Abu Khadra, Ahmad M Aljaberi, Marwan H Gagaa, Hamzah S Issa
Abstract : Hazardous health effects resulting from exposure to radiofrequency electromagnetic radiation (RF-EMR) emitted from cell phones have been reported in the literature. However, the cellular and molecular targets of RF-EMR are still controversial. The aim of this study was to examine the oxidant/antioxidant status in saliva of cell phone users. Saliva samples collected before using a cell phone as well as at the end of 15 and 30 min calls were tested for two commonly used oxidative stress biomarkers: malondialdehyde (MDA) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-Oxo-dG). The 8-oxo-dG levels were determined by enzyme-linked immunosorbent (ELISA) competitive assay, while the MDA levels were measured using the OxiSelect MDA adduct ELISA Kit. The antioxidant capacity of the saliva was evaluated using the oxygen radical absorption capacity (ORAC) and the hydroxyl radical averting capacity (HORAC) assays according to the manufacture instructions. The mean 8-oxo-dG and the Bradford protein concentrations (ng/ml and mg/ml, respectively) peaked at 15 min. The levels of HORAC, ORAC and MDA progressively increased with time and reached maximum at 30 min. However, there was no significant effect of talking time on the levels of 8-OxodG and MDA. Similarly, there was no statistically significant effect of talking time on the oxygen and hydroxyl radicals averting capacities, (ORAC) and (HORAC), respectively. These findings suggest that there is no relationship between exposure to radio frequency radiation (RFR) and changes in the salivary oxidant/antioxidant profile.
Keywords : Antioxidant activity, cell phone, oxidative stress biomarkers, saliva
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Tableting functionality evaluation of Prosolv Easytab in comparison to physical mixtures of its individual components
Authors : Ahmad Aljaberi, Adel Ardakani, Ayman Khdair, Safwan A. Abdel-Rahim, Eman Meqdadi, Manal Ayyash, Ghada Alobaidi, Nizar Al-Zoubi
Abstract : Prosolv Easytab is a recently introduced all-in-one excipient for direct compression. The aim of this work was to compare the compaction and dissolution functionalities of Prosolv Easytab versus equivalent physical mixtures of microcrystalline cellulose (MCC) or silicified microcrystalline cellulose (Prosolv SMCC) with complementary excipients. Lutrol F68 was used as a free flowing and poorly compactable model material for the comparison of the compaction functionality, and carbamazepine was used as a poorly soluble model drug for the investigation of the dissolution rate and dissolution stability after storage under accelerated stability conditions. Results showed that Prosolv Easytab produced comparable compatibility, dissolution and dissolution stability to its analogous physical mixtures based on MCC or Prosolv SMCC. The current findings suggest that Prosolv Easytab is functionally equivalent to physical mixture of its components, with obvious advantages regarding simplicity of manufacture and the potential masking of undesirable properties of individual components.
Keywords : Prosolv Easytab , Prosolv SMCC , Microcrystalline cellulose , Silicified microcrystalline cellulose , Co-processed excipients , Compactibility.
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Anthropometric measures as predictors for the occurrence of insulin resistance among obese Jordanians
Authors : Khalid M. Abu khadra and Ahmad Aljaberi
Abstract : A total of 210 overweight and obese participants were recruited to investigate the association between various obesity parameters with insulin resistance (IR) in Jordanians. Weight, height, waist circumference (WC) and hip circumference were measured, and the corresponding body mass index (BMI), waist to hip ratio (WHR), and waist to height ratio (WHtR) were calculated. HOMA-IR was calculated from the corresponding fasting blood sugar and plasma insulin levels for each participant. The correlation as well as the prediction ability of obesity parameters for the occurrence of insulin resistance was evaluated statistically. Pearson and point-biserial correlation coefficients revealed that only BMI, WC and WHtR correlated with insulin resistance. However, the strength of correlation appeared to be gender-dependent. Logistic regression and ROC curve analysis showed that BMI is the best parameter to predict insulin resistance in the male population followed by WHtR. In females however, WHtR appeared to be a better classifier than BMI. In conclusion, BMI and WHtR were found to be the most significant obesity parameters for predicting insulin resistance in Jordanians male and female populations, respectively.
Keywords : Obesity, body mass index, waist circumference, waist to height ratio, insulin resistance.
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