الفهرس 
Title : Formulation and evaluation of certain fast dissolving dosage forms for A model drug
ContentsOnly 14 pages are availabe for public view
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Abstract
Disturbed sleep can causeto many health problems such as cognitive impairment, depressed mood, and negative effects on cardiovascular, endocrine, and immune function. This study formulates and optimizes Eszopiclonetrilaminate fast dissolving film.
Prepared Eszopiclonetrilaminate fast dissolving film (Eszopiclone TFDF) was characterized by disintegration time, drug release, tensile strength (TS), percentage elongation (EB%), folding endurance, taste masking test, and in vitro dissolution test. The selected formulas were F2 (0.5% xanthan gum, 10% propylene glycol), F4 (3% sodium alginate, 10% propylene glycol) and F6 (1.5% pullulan, 10% propylene glycol) were subjected to in vivo study compared to conventional Lunesta® tablet.
The results indicated that disintegration time was in the range of 9 to 40 sec. Drug release was found to be in the range of 78.51%–99.99%, while TS values and EB% differed from 11.12 to 25.74 (MPa) and 25.38%–36.43%, respectively. The folding endurance went between 200 and 300 times. All formulas exhibited acceptable uniformity content, surface pH, film thickness, and a good taste feeling.
F4 had the highest Cmax (39.741 ± 6.785-μg/l) and lower Tmax (1.063 hr) among other formulas and conventional tablets. Therefore, FDFs’ technology could increase the therapeutic effect of Eszopiclone.
This thesis aimed to formulate, evaluate, and optimize different Eszopiclone-FDFs. Formulation variables affecting FDF properties were studied to the plain FDFs in the preliminary study. The chosen formulae were then used to formulate tri-laminatedEszopiclone–FDFs. Then the trilaminatedEszopiclone –FDFs were evaluated and from them the best three formulae were incorporatedin the in vivo study.
Anin-vivo study in humans was carried out to assess the pharmacokinetic parameters and relative bioavailability (RB) of Eszopiclonein the tri-laminated FDFs compared to the marketed product (Lunesta®).
Therefore, the work in this thesis was divided into two chapters:
Chapter I: Formulation, evaluation and optimization of tri-laminated fast dissolving films containing Eszopiclone
Chapter II:In-vivo pharmacokinetic study of the selected tri-laminated fastdissolving films containing Eszopiclone.
Chapter I: Formulation, evaluation and optimization of tri-laminated fast dissolving films containing Eszopiclone
This chapter aimed to formulate, evaluate, and optimize different tri-laminated Eszopiclone-FDFsviathe solvent casting technique. The optimum tri-laminated Eszopiclone -FDFs were selected according to the criteria of scoring: the fastest disintegration time (DT) and highest % Eszopiclonereleased. They were then subjected to taste masking test.
This chapter’s investigations and findings can be summarized as follows:
• The spectrophotometric scanning of Eszopiclonein SSF (pH 6.8) was done and showed λmax at 304 nm.
• The DSC analysis of pure Eszopicloneand the physical mixture of Eszopiclonewith excipients were done and showed no incompatibility.
• The formulation and optimization of plain-FDFs were carried out by fast dissolving technique from which best formulae were selected to formulate tri-laminated Eszopiclone –FDFs.
• Eight FDFs were the outcome of the preliminary study.
• The eighttri-laminated Eszopiclone –FDFs were formulated and each layer from the three layers were merged to each other using casting solvent.
• The tri-laminated Eszopiclone –FDFswere evaluated in terms of film thickness, surface pH, folding endurance, drug content, in-vitro disintegration time, drug release, and taste masking test.
• The films were transparent, colorless, thin, and smooth.
• The thickness values of the Eszopiclone –FDFsranged from 0.23±0.05 to 0.28±0.02mm.
• All films showed a folding endurance value of up to 300 folds, which indicates good film flexibility.
• All films had a surface pH close to the salivary pH (6.8), ranging from 6.5-6.8.
• The assay of drug content of all Eszopiclone –FDFswas within the compendia specifications as it lies in the range between 97±0.03% to 109±0.03% and this indicates the uniform distribution of the drug in the film.
• The disintegration time of all eight formulae ranging from 9 ± 0.02 to 40 ± 0.05 sec.
• Based on the in vitro evaluation results the pullulan-based FDF, sodium alginate-based FDF and xanthan-based FDFwere chosenas the optimum formulae as they scored the fastest DT and the highest folding endurance for in vivo study.
• The taste masking test (human panel testing) was done to the three tri-laminated selected formulae. All three formulae are pleasant.
Chapter II: In-vivo pharmacokinetic study of the selected tri-laminated fast dissolving films containing Eszopiclone.
This chapter aimed to assess the pharmacokinetic parameters and relative bioavailability of Eszopiclonefrom the tri-laminated FDFs (F2, F4, and F6) in humans compared to the marketedtablets (Lunesta®, 1mg).
This chapter’s investigations and findings can be summarized as follows:
• LC-MS/MS was a suitable method for the analysis of Eszopiclonein human plasma.
• The mean values of Cmax, Tmax,AUC (0-48), and AUC (0-∞) were calculated.
• The mean values of Cmaxand AUC (0-∞)of the three tri-laminated FDFs were significantly (p<0.05)higher than that of the marketed products (Lunesta®).
• The mean value ofTmaxof the three tri-laminated FDFs were significantly (p<0.05) shorter than that of the marketed products.
• Based on the AUC (0-∞), Tmax, and the Cmaxvalues, the F4FDFattained the best results compared to the marketed product.
• The higher Cmax, the smaller Tmax and the faster absorption rate of the three selected formula compared to the marketed product might be due to that the drug was partially absorbed via the oral mucosa and evades first-pass metabolism.