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Al-Hayali, Amani Ibraheem YounisORCID iD iconorcid.org/0000-0002-2273-457x
Alternative names
Publications (7 of 7) Show all publications
AlHayali, A., Vuddanda, P. R. & Velaga, S. (2019). Silodosin oral films: Development, physico-mechanical properties and in vitro dissolution studies in simulated saliva. Journal of Drug Delivery Science and Technology, 53, Article ID 101122.
Open this publication in new window or tab >>Silodosin oral films: Development, physico-mechanical properties and in vitro dissolution studies in simulated saliva
2019 (English)In: Journal of Drug Delivery Science and Technology, ISSN 1773-2247, Vol. 53, article id 101122Article in journal (Refereed) Published
Abstract [en]

Sublingual film dosage forms for drugs used for fast symptomatic treatment have promise because they allow a rapid onset of action. The aim of this study was to prepare films of silodosin intended for sublingual administration for the symptomatic treatment of benign prostatic hyperplasia in men. Hydroxypropyl methylcellulose (HPMC) or hydroxypropyl methylcellulose acetate succinate (HPMC-AS) were used as film-forming polymers. The effects of the polymers and the surfactant tocopherol polyethylene glycol succinate (TPGS) on the physico-mechanical properties and dissolution behavior of the films in simulated saliva were investigated. The eight silodosin oral films developed (F1–F8) contained 8 mg silodosin per 6 cm2 film and HPMC or HPMC-AS in drug:polymer ratios of 1:5 or 1:3, while four also contained TPGS (0.5% w/w). The films were characterized using DSC, TGA, SEM, and PXRD and the mechanical properties were investigated by measuring tensile strength, elongation at break and Young's modulus. The mechanical properties of the films were dependent on the ratio of polymer used. The in vitro dissolution and drug release studies indicated that HPMC-AS films disintegrated more quickly than HPMC films. Silodosin was shown to be dispersed within the polymers. Despite silodosin being submicronized in the HPMC films, the dissolution and drug release rate (time for 80% release) from HPMC films was significantly faster than from HPMC-AS films. TPGS increased the drug release rate to a greater extent with HPMC than with HPMC-AS. The degree of saturation of formulation F4 was >1, which shows potential for improving oral absorption of silodosin.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Silodosin, Sublingual oral films, HPMC, HPMC-AS, TPGS, Simulated saliva
National Category
Other Health Sciences
Research subject
Health Science
Identifiers
urn:nbn:se:ltu:diva-75248 (URN)10.1016/j.jddst.2019.06.019 (DOI)000487963600019 ()
Note

Validerad;2019;Nivå 2;2019-07-08 (johcin)

Available from: 2019-07-08 Created: 2019-07-08 Last updated: 2019-10-18Bibliographically approved
AlHayali, A. (2018). In vitro-solubility and supersaturation behavior of supersaturating drug delivery systems. (Doctoral dissertation). Luleå: Luleå University of Technology
Open this publication in new window or tab >>In vitro-solubility and supersaturation behavior of supersaturating drug delivery systems
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
In vitro-löslighet och övermättningsegenskaperhos övermättat läkemedels-administrationssystem
Abstract [en]

The development of new pharmaceutical products has been challenged by the growing number of poorly water-soluble drugs, which often lead to suboptimal bioavailability. Various approaches, such as the use of amor-phous solid dispersions and cocrystals, have been used to improve the solu-bility, and subsequent bioavailability, of these drug molecules. Supersaturat-ing drug delivery systems (SDDSs) have potential for achieving adequate oral drug bioavailability by increasing the drug solubility and creating a su-persaturated state in the gastrointestinal tract. However, there is a need for better understanding of the supersaturation behavior in SDDSs and of the factors affecting supersaturation. The main objective of this thesis was to improve understanding of the supersaturation solubility behavior in SDDSs with a particular focus on rapidly dissolving solid forms (amorphous forms/cocrystals).

In the course of the work, a new formulation for ezetimibe using an amorphous solid dispersion was prepared, cocrystals of tadalafil were pre-pared, and oral films of silodosin were formulated for the first time. These new formulations were thoroughly characterized using a number of solid-state and pharmaceutical characterization techniques.

The dissolution and supersaturation behavior of the prepared SDDSs were studied. The effects of various factors on the supersaturation and precipita-tion characteristics were investigated. These factors included the preparation method, the temperature of the dissolution medium, the type of dissolution biorelevant medium (gastric/intestinal) used, the permeability of the relevant gastrointestinal membranes, the addition of polymers, and the addition of surfactants. The amorphous solid dispersions, cocrystals and oral films that were prepared represent new drug formulations that provide significantly higher dissolution rates and supersaturated solubility than crystalline drug forms. Solid dispersions prepared by the melting method had better super-saturation properties than those prepared by spray drying. The precipitation kinetics of the solid dispersion were faster at 37 ̊C than at 25 ̊C in bio-relevant media. Implementation of an absorption tool during in vitro evalua-tion of supersaturation levels could improve the prediction accuracy of su-persaturation and precipitation. A better understanding of the effects of ex-cipients on the supersaturation and precipitation behavior of these types of formulation was obtained in this thesis. The improvement in supersaturation solubility obtained by adding polymers and surfactants was not proportional to the amounts of excipient used.

This thesis has made notable contributions to the field of pharmaceutical science by advancing our understanding of the supersaturation solubility behavior of the newly prepared SDDSs.

Place, publisher, year, edition, pages
Luleå: Luleå University of Technology, 2018
Series
Doctoral thesis / Luleå University of Technology 1 jan 1997 → …, ISSN 1402-1544
National Category
Other Health Sciences
Research subject
Health Science
Identifiers
urn:nbn:se:ltu:diva-68787 (URN)978-91-7790-154-9 (ISBN)978-91-7790-155-6 (ISBN)
Public defence
2018-06-19, D770, Luleå, 10:00 (English)
Opponent
Supervisors
Available from: 2018-05-18 Created: 2018-05-18 Last updated: 2018-06-08Bibliographically approved
AlHayali, A., Selo, M. A., Ehrhardt, C. & Velaga, S. (2018). Investigation of supersaturation and in vitro permeation of the poorly water soluble drug ezetimibe. European Journal of Pharmaceutical Sciences, 117, 147-153
Open this publication in new window or tab >>Investigation of supersaturation and in vitro permeation of the poorly water soluble drug ezetimibe
2018 (English)In: European Journal of Pharmaceutical Sciences, ISSN 0928-0987, E-ISSN 1879-0720, Vol. 117, p. 147-153Article in journal (Refereed) Published
Abstract [en]

The interplay between supersaturation, precipitation and permeation characteristics of the poorly water-soluble drug ezetimibe (EZ) was investigated. Supersaturation and precipitation characteristics of EZ in the presence of Caco-2 cells were compared to those in a cell-free environment. The effect of the water-soluble polymer polyvinyl pyrrolidone (PVP-K30) on the supersaturation, precipitation and transport of EZ was also investigated and the amount of drug taken up by Caco-2 cells was quantified.

A one-compartment setup without Caco-2 cells (i.e. in the wells of cell-culture plates) was used to mimic a non-sink in vitro dissolution chamber. The two-compartment Caco-2 cell monolayer setup (with apical and basolateral compartments) was used to investigate how the absorption of EZ affects supersaturation. EZ in varying degrees of supersaturation (DS; 10, 20, 30 and 40) was introduced into the one-compartment setup or the apical chamber of the two-compartment setup. Samples were collected at specific times to determine supersaturation, precipitation and permeation. At the end of the study, Caco-2 cells were lysed and the intracellular amount of EZ was quantified.

In the one-compartment setup, a high DS was associated with rapid precipitation. Supersaturation was maintained for longer time periods and precipitation was lower in the presence of Caco-2 cells. There were no significant differences in the absorption rate of the drug, even at high concentrations on the apical side. Permeability coefficients for all supersaturated solutions (i.e. DS 10–40) were significantly (p < 0.05) different from those when EZ was present in crystalline form. Both concentrations of PVP-K30 (i.e. 0.05% and 0.1% w/v) improved solubility and supersaturation of EZ when added to the apical side, however, the increase in absorption at the higher concentration was not proportional. The amount of intracellular EZ increased with increasing DS in the apical side, until the saturation limit was reached in the cells (i.e. at DS 30 and higher).

This study demonstrated that precipitation of EZ could be overestimated when supersaturation was investigated without the implementation of an absorption compartment in vitro, both in the absence and in the presence of polymer.

Place, publisher, year, edition, pages
Elsevier, 2018
National Category
Other Health Sciences
Research subject
Health Science
Identifiers
urn:nbn:se:ltu:diva-67527 (URN)10.1016/j.ejps.2018.01.047 (DOI)000430368800018 ()29408604 (PubMedID)2-s2.0-85042182339 (Scopus ID)
Note

Validerad;2018;Nivå 2;2018-03-01 (andbra)

Available from: 2018-02-06 Created: 2018-02-06 Last updated: 2019-03-27Bibliographically approved
Shimpi, M. R., Al-Hayali, A., Cavanagh, K. L., Rodríguez- Hornedo, N. & Velaga, S. P. (2018). Tadalafil-malonic acid cocrystal: Physicochemical characterization, pH-solubility and supersaturation studies. Crystal Growth & Design, 18(8), 4378-4387
Open this publication in new window or tab >>Tadalafil-malonic acid cocrystal: Physicochemical characterization, pH-solubility and supersaturation studies
Show others...
2018 (English)In: Crystal Growth & Design, ISSN 1528-7483, E-ISSN 1528-7505, Vol. 18, no 8, p. 4378-4387Article in journal (Refereed) Published
Abstract [en]

The purpose of this study was to enhance the solubility and dissolution of a poorly water-soluble drug, tadalafil (TDF), by cocrystal formation with malonic acid (MOA), to characterize the cocrystal structure, and to quantify the cocrystal solution behavior. The crystal structure revealed a 1:1 stoichiometry wherein the TDF molecules form a double layered structure through N–H…O=C interactions linked to a catemeric chain of MOA molecules via O-H…O hydrogen bonds. Cocrystal solubility advantage (SA defined as Scocrystal/Sdrug) or supersaturation index was determined from eutectic point measurements to be 102 to 129 in the pH range of 1 to 3. Cocrystal dissolution generated supersaturation levels (Cmax/Sdrug) of 30 in buffer and 120 in the presence of a nucleation inhibitor, HPMC. The amorphous form of TDF generated supersaturation 3 times lower than cocrystal in buffer, and not significantly different from cocrystal in the presence of HPMC. Thus, supersaturation index is a valuable metric for assessing the risk of cocrystal conversion during kinetic studies and for predicting conditions when the usage of a precipitation inhibitor may significantly increase cocrystal exposure levels.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2018
National Category
Other Health Sciences Physical Chemistry
Research subject
Health Science; Chemistry of Interfaces
Identifiers
urn:nbn:se:ltu:diva-69663 (URN)10.1021/acs.cgd.8b00362 (DOI)000440956100024 ()
Note

Validerad;2018;Nivå 2;2018-08-02 (rokbeg)

Available from: 2018-06-19 Created: 2018-06-19 Last updated: 2019-09-23Bibliographically approved
Al-Hayali, A. I., Tavellin, S. & Velaga, S. (2017). Dissolution and precipitation behavior of ternary solid dispersions of ezetimibe in biorelevant media (ed.). Drug Development and Industrial Pharmacy, 43(1), 79-88
Open this publication in new window or tab >>Dissolution and precipitation behavior of ternary solid dispersions of ezetimibe in biorelevant media
2017 (English)In: Drug Development and Industrial Pharmacy, ISSN 0363-9045, E-ISSN 1520-5762, Vol. 43, no 1, p. 79-88Article in journal (Refereed) Published
Abstract [en]

The effects of different formulations and processes on inducing and maintaining the supersaturation of ternary solid dispersions of ezetimibe (EZ) in two biorelevant media fasted-state simulated intestinal fluid (FaSSIF) and fasted-state simulated gastric fluid (FaSSGF) at different temperatures (25˚C and 37˚C) were investigated in this work. Ternary solid dispersions of EZ were prepared by adding polymer PVP-K30 and surfactant poloxamer 188 using melt-quenching and spray-drying methods. The resulting solid dispersions were characterized using scanning electron microscopy, differential scanning calorimetry, modulated differential scanning calorimetry, powder X-ray diffraction and Fourier transformation infrared spectroscopy. The dissolution of all the ternary solid dispersions was tested in vitro under non-sink conditions. All the prepared solid dispersions were amorphous in nature. In FaSSIF at 25˚C, the melt-quenched (MQ) solid dispersions of EZ were more soluble than the spray-dried solid (SD) dispersions and supersaturation was maintained. However, at 37˚C, rapid and variable precipitation behavior was observed for all the MQ and SD formulations. In FaSSGF, the melting method resulted in better solubility than the spray-drying method at both temperatures. Ternary solid dispersions show potential for improving solubility and supersaturation. However, powder dissolution experiments of these solid dispersions of EZ at 25˚C may not predict the supersaturation behavior at physiologically relevant temperatures.  

Place, publisher, year, edition, pages
Taylor & Francis, 2017
National Category
Other Health Sciences
Research subject
Health Science
Identifiers
urn:nbn:se:ltu:diva-10634 (URN)10.1080/03639045.2016.1220566 (DOI)000394022300009 ()27487184 (PubMedID)2-s2.0-84984655366 (Scopus ID)97717bba-7cba-45dd-96f0-e41d826a95ac (Local ID)97717bba-7cba-45dd-96f0-e41d826a95ac (Archive number)97717bba-7cba-45dd-96f0-e41d826a95ac (OAI)
Note

Validerad; 2017; Nivå 2; 2017-01-30 (andbra)

Available from: 2016-09-29 Created: 2016-09-29 Last updated: 2018-11-15Bibliographically approved
Al-Hayali, A., Selo, M. A., Ehrhardt, C. & Velaga, S. (2017). Investigation of supersaturation and permeation of a poorly water soluble drug Ezetimibe: Systems approaches to drug discovery, development and clinical usage. In: Future Medicines For One World: . Paper presented at 6th FIP Pharmaceutical Sciences World Congress 2017, Stockholm, Sweden, 21-24 May 2017.
Open this publication in new window or tab >>Investigation of supersaturation and permeation of a poorly water soluble drug Ezetimibe: Systems approaches to drug discovery, development and clinical usage
2017 (English)In: Future Medicines For One World, 2017Conference paper, Poster (with or without abstract) (Refereed)
National Category
Medical and Health Sciences Other Health Sciences
Research subject
Health Science
Identifiers
urn:nbn:se:ltu:diva-64396 (URN)
Conference
6th FIP Pharmaceutical Sciences World Congress 2017, Stockholm, Sweden, 21-24 May 2017
Note

OBS

Available from: 2017-06-22 Created: 2017-06-22 Last updated: 2018-04-16Bibliographically approved
Al-Hayali, A. I., Tavelin, S. & Velaga, S. (2014). Dissolution and precipitation behavior of ternary solid dispersions of Ezetimibe in biorelevant media: AAPS annual meeting and Exposition2014 USA (ed.). In: (Ed.), : . Paper presented at AAPS Annual Meeting and Exposition : 02/11/2014 - 06/11/2014.
Open this publication in new window or tab >>Dissolution and precipitation behavior of ternary solid dispersions of Ezetimibe in biorelevant media: AAPS annual meeting and Exposition2014 USA
2014 (English)Conference paper, Poster (with or without abstract) (Other academic)
Abstract [en]

PurposeTo prepare ternary solid dispersions of Ezetimibe (EZ) and investigate their powder dissolution and precipitation behavior(supersaturation) in simulated gastric and intestinal fluidsMethodsTernary solid dispersions of EZ were prepared with PVPK30 and Poloxamer 188 at different ratios. Spray drying and meltquenching methods were used for the preparation of these solid dispersions. The solid dispersions were characterized bybasic to advanced solid-state tools including Modulated differential scanning calorimetry (MDSC), Powder X-ray diffractionand Fourier transform infrared spectroscopy .Biorelevant simulated media (FaSSIF pH 6.5 and FaSSGF pH1.6) were used tostudy the supersaturating solubility of the ternary solid dispersions. HPLC was used to determine the drug concentrationsResultsTernary solid dispersions were successfully prepared by spray drying and melt quench methods. All prepared soliddispersions showed broadening of the XRD peaks indicating amorphous nature. MDSC analysis revealed disappearance ofthe melting peak of Ezetimibe indicating that molecular dispersion of the drug in polymer matrix. The solid dispersions withhigher PVPK30 content showed single Tg at 158.54 °C (spray drying) and 169.32 °C (melt quench). About 10 folds increasein the apparent solubility was observed for solid dispersions prepared by both methods. However, melt quenched soliddispersions had maintained the supersaturation solubility in FaSSIF longer than spray dried solid dispersions. Dissolutionstudies in FaSSGF are ongoingConclusionAmorphous ternary solid dispersions of Ezetimibe containing PVP K30 and Poloxamer 188 could be prepared by spraydrying and melt quenching methods. These solid dispersions showed improved solubility and prolonged supersaturation inbiorelevant media

National Category
Other Health Sciences
Research subject
Health Science
Identifiers
urn:nbn:se:ltu:diva-28058 (URN)1b64f18a-f4dd-4068-8c13-ae4b154ec0bf (Local ID)1b64f18a-f4dd-4068-8c13-ae4b154ec0bf (Archive number)1b64f18a-f4dd-4068-8c13-ae4b154ec0bf (OAI)
Conference
AAPS Annual Meeting and Exposition : 02/11/2014 - 06/11/2014
Note

Godkänd; 2014; 20141209 (amayou)

Available from: 2016-09-30 Created: 2016-09-30 Last updated: 2018-04-16Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-2273-457x

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