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العنوان
Formulation of Fast Dissolving Dosage Forms for Taste Masking /
المؤلف
Al-Azhary, Amr Mahmoud.
هيئة الاعداد
باحث / Amr Mahmoud Al-Azhary
مشرف / ABD AL-HAMEED AL-SHAMEY
مشرف / GEHANNE ABDEL SAMIE AWAD
مناقش / MAHMOUD EID SOLIMAN
تاريخ النشر
2016.
عدد الصفحات
205 P. :
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
الصيدلة ، علم السموم والصيدلانيات (المتنوعة)
تاريخ الإجازة
1/1/2016
مكان الإجازة
جامعة عين شمس - كلية الصيدلة - قسم الصيدلانيات
الفهرس
Only 14 pages are availabe for public view

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Abstract

This study aimed to develop orodispersible powder (ODP) for administration without the need for water with taste masked and enhanced dissolution properties using ibuprofen (IBP) as a model drug. A solid dispersion of IBP in the polymeric carrier was prepared using spray dried dispersions (SDD) technique. IBP induced sensation (chemesthesis) was masked using binary polymeric carrier composed of Eudragit EPO as chemesthesis masking polymer and PVP K30 as a glass transition temperature (Tg) support polymer. The selected formula was loaded on fast dissolving, porous, large particle size spheroids composed of dextrates (EMDEX®). The loaded taste masked microparticles are filled into stick packs for direct-to-mouth administration. This would enable achieving faster onset of action (pain relief) in vivo, convenience of use, and improving patient compliance.
Hence, the work in this thesis was divided into three chapters:
Chapter I: Optimization of Spray Drying for Taste Masking of Ibuprofen
This chapter aimed to mask the IBP chemesthetic sensation (throat scratch) via the formation of SDD in a polymeric carrier composed of Eudragit® EPO (E-EPO) and poly vinyl pyrrolidone (PVP K30). E-EPO is a cationic copolymer based on dimethylaminoethyl methacrylate, butyl methacrylate, and methyl methacrylate copolymer with a pH dependent solubility, specifically designed for taste masking. It is soluble in gastric fluid up to pH 5.0 and Swellable and permeable above pH 5.0, while PVP K30 is used as Tg supporting polymer for enhanced SDD physical stability and processability. The spray solution was prepared by dissolving IBP at different ratios (25, 30 and 35%) and E-EPO and PVP K30 at weight % ratios: 20:80, 30:70, 40:60 and 50:50 of the total polymeric content in organic solvent composed of acetone /dichloromethane (70:30 v/v). The spray drying process design methodology provided a link between the data generated by thermodynamic model and the predicted formulation attribute; glass transition temperature (Tg). The thermodynamic space was created from the data generated from spray drying model as a response to a wide range of entered inlet temperatures (TIN), the corresponding outlet temperatures (TOUT) and outlet relative solvent saturation (%RSOUT). Processing parameters constraints of spray drying of SDDs were set following a systematic approach for determining inlet temperature by using sticky point curve and composition-temperature phase diagram of the solvent mixture used. The corresponding TOUT and % RSOUT were then generated by the model. The process design spaces were then obtained by applying processing parameters constraints to the thermodynamic spaces. The prepared spray solutions were spray dried according to the design space where the collected SDD were characterized. The yield of the spray drying process was dependent on the Tg of each formula, where the yield increases with increased Tg values. The SDDs stored at ambient conditions in a desiccator were examined visually for physical powder form stability over 6 months, where formulae F5-F10 were excluded due to the formation of aggregates. The taste results revealed that F3 (25% IBP in polymeric carrier composed of E-EPO: PVP K30 at 40:60 w/w ratio) and F4 (25% IBP in polymeric carrier composed of E-EPO: PVP K30 at 50:50 w/w ratio) were taste masked initially. It was found that after 6 months of storage at desiccator F3 failed to maintain chemesthesis masking effect. The solid state of the selected formula (F4) revealed that that IBP is converted into a molecular or amorphous state as proved by FTIR (disruption of dimeric IBP-IBP hydrogen bonding), loss of crystallinity was evident from DSC and XRD. The dissolution of IBP from F4 in pH 1.2 showed a significant enhancement of the selected formula over physical mixture and unprocessed IBP. The nitrogen proportion of the F4 microspheres was characterized by energy dispersive X- ray analysis (EDX) and elemental analysis (CHN). The microanalysis of F4 revealed a lower nitrogen proportion at the surface compared to the total elemental nitrogen content which could indicate microparticle surface enrichment with E-EPO. Micromeritic studies on F4 formula showed bulk density of about 0.2 g/mL and passable flow properties.
Chapter II: Preparation and characterization of Orodispersible Powder (ODP) Containing the Optimized Taste Masked Ibuprofen Spray Dried Powder
This chapter aimed to prepare orodispersible powder (ODP) for direct-to-mouth administration without the need for water. Two suggested carriers; dextrates (EMDEX®) and Pharmasperse® 416 a co-processed calcium carbonate and polyols. The selected formula (F4) was mixed with either EMDEX® or Pharmasperse® 416 (1:3 w/w ratios), but in case of EMDEX® based formula starch and fumed silica were additionally required. The taste of both ODP formulations were taste masked but it was observed that F4-Pharmasperse based ODP left soft residues after swallowing and so it was excluded from further studies. F4- EMDEX exhibited 96.2% IBP release in pH 1.2 dissolution media in first five minutes in comparison to 75.3% F4 without EMDEX® Additionally the flow micromertics of F4-EMDEX were found excellent and densification was more than 2.4-fold compared to F4. The scanning electron microscopy micrographs revealed diffusion of F4 microspheres into pores of EMDEX.
Chapter III: Pharmacokinetic Studies on the selected Ibuprofen Orodispersible Powder (F4-EMDEX)
In chapter 3, the pharmacokinetics of IBP was determined after oral administration to albino rats of F4-EMDEX (F4: EMDEX® at 1:3 w/w) and commercial Brufen® Granules.
The plasma pharmacokinetic parameters of F4-EMDEX showed enhanced Tmax of 0.306 h compared to 0.75 h of the same dose of Brufen® Granules. The Cmax of F4-EMDEX and Brufen® Granules were 44.967 and 41.467 µg/mL respectively. The AUC (0-∞) of F4-EMDEX were 115.398 µg/mL.h compared to 130.790 µg/mL.h in commercial IBP. The t1/2 of F4-EMDEX was 3.794 h while commercial IBP was 4.290 h. The mean residence time (MRT) in plasma were 4.969 and 5.472 h for F4-EMDEX and Brufen® Granules respectively.
Keywords: Ibuprofen; Spray dried dispersion (SDD); glass transition temperature; thermodynamic model; sticky point curve; temperature – composition phase diagram; thermodynamic space; design space; chemesthesis; taste masking; orodispersible powder (ODP); ordered mixture; dissolution enhancement, Dextrates (EMDEX®).