Hydrogel-forming microneedles enhance transdermal delivery of metformin hydrochloride, Journal of controlled release 285, 142-151,2018
Authors : Eman M. Migdadi , Aaron J. Courtenay , Ismaiel A. Tekko a, Maelíosa T.C. McCrudden ,Mary-Carmel Kearney , Emma McAlister , Helen O. McCarthy , Ryan F. Donnelly
Abstract : We investigated, for the first time, the potential for a hydrogel-forming microneedle (MN) patch to deliver the high-dose drug metformin HCl transdermally in a sustained manner. This may minimize some gastrointestinal side effects and small intestine absorption variations associated with oral delivery. Patches (two layers) were assembled from a lyophilised drug reservoir layer, with the MN layer made from aqueous blend of 20% w/w poly (methylvinylether-co-maleic acid) crosslinked by esterification with 7.5% w/w poly (ethylene glycol) 10,000 Da. >90% of metformin was recovered from homogeneous drug reservoirs. Drug reservoir dissolution time in PBS (pH 7.4) was <10 min. MN penetrated a validated skin model Parafilm® M consistently. Permeation of metformin HCl across dermatomed neonatal porcine skin in vitro was enhanced by using MN. The combined MN and metformin HCl reservoir patch (containing 75 mg or 50 mg metformin HCl, respectively) delivered 9.71 ± 2.22 mg and 10.04 ± 1.92 mg at 6 h, respectively, and 28.15 ± 2.37 mg and 23.25 ± 3.58 mg at 24 h, respectively.In comparison, 0.34 ± 0.39 mg and 0.85 ± 0.68 mg was delivered at 6 h, respectively, and 0.39 ± 0.39 mg and 1.01 ± 0.84 mg was delivered at 24 h, respectively, from a control set-up employing only the drug reservoirs. In vivo, metformin HCl was detected in rat plasma at 1 h post MN application at a concentration of 0.62 ± 0.51 μg/mL, increasing to 3.76 ± 2.58 μg/ml at 3 h. A maximal concentration of 3.77 ± 2.09 μg/ml was achieved at 24 h. Css was 3.2 μg/mL. Metformin transdermal bioavailability using MNs was estimated as 30%.Hydrogel-forming MN are a promising technology that has demonstrated successful transdermal delivery of metformin HCl. Potential clearly exists for administration of other high-dose drugs using this system.
Keywords : Metformin HCl, Hydrogel-forming microneedles, Transdermal delivery
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Tableting functionality evaluation of Prosolv Easytab in comparison to physical mixtures of its individual components. J. Drug Deliv. Sci. Technol, 23, 499-504, 2013
Authors : A Aljaberi, A Ardakani, A Khdair, SA Abdel-Rahim, E Meqdadi, M Ayyash
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 équivalent 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 compactibility, 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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siRNA as a potential therapy for COVID-19. Current Drug Delivery, 2021
Authors : A Aljaberi, EM Migdadi, K Khadra, MA Samak, IA Basheti, N 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 to as much individuals as possible. The genome of SARS-CoV2 share 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 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; Respiratory; SARS-CoV2; siRNA
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Impact of the manufacturing technique on the dissolution-enhancement functionality of PEG4000 in Cilostazol tablets. Pharmacia 68, 243, 2021
Authors : O Sawafta, S Alhadid, IAA Awwad, E Migdadi, A 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 PEG4000during 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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