الفهرس 
Abstract
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Abstract
Abstract
Progesterone (PG) is a natural female sex hormone, secreted by the corpus luteum and placenta. It is essential for maintenance of pregnancy in case of habitual or threatened abortion. It is also used as an oral contraceptive. Moreover, it has several other uses such as hormone replacement therapy.
Several gynecological conditions were either corrected or treated using oral synthetic progesterone. However, the androgenic activity of these synthetic compounds minimizes its extensive use in reproductive technology because of the risk of teratogenic effects. Natural progesterone is free of any androgenic activity that might affect lipoprotein metabolism or induce teratogenicity.
Progesterone is available commercially as oral soft gelatin capsules and intramuscular (I.M.) injection in dose of 100 mg. Also it is available as vaginal tablets and suppositories. Natural PG has a very low bioavailability (" ~ " 25%) when it is given orally since it is a hydrophobic drug, has a very short elimination half-life (" ~ "19-95 min) and undergoes extensive metabolism by the liver. In addition, oral administration of large doses is associated with several unwanted GI adverse effects such as diarrhea and abdominal pain. As a result, intramuscular (IM) injection and vaginal formulations are currently used to overcome the shortcomings of oral PG.
Vaginal delivery of PG has several advantages such as avoidance of hepatic first-pass metabolism, lack of local pain, the reduction in the incidence of gastrointestinal side effects, high bioavailability and local endometrial effect. However the conventional vaginal dosage forms suffer from many problems derived from their poor retention time at site of action. This causes deficient dosages and thus, multiple daily doses are often required, leading to decreased patient acceptability.
Recently, to overcome the limitations associated with conventional vaginal formulations, researches have focused their attention on the development new alternative delivery systems in order to provide long-term therapeutic action at absorption site and thus leading to improved bioavailability and reduced dosing frequency.
Accordingly, this study has aimed to formulate mucoadhesive tablets that can deliver progesterone into the vaginal cavity in an attempt to avoid first pass hepatic metabolism, prolong the residence time of PG on the vaginal mucosa and hence improve therapeutic efficacy, patient compliance and to overcome the drawbacks of the conventional dosage forms. However, progesterone has a very poor aqueous solubility which limits the dissolution prior to its absorption and consequently could limit its bioavailability. So, solid dispersion technique with certain water soluble carriers and complexation with cyclodextrins were approached to improve the aqueous solubility and dissolution of PG.
• Thus, the work in this thesis is divided into three parts
Part I: Enhancement of progesterone (PG) aqueous solubility and dissolution rate using different techniques such as solid dispersion, inclusion complex and micellar solubilization.
Part II: Formulation and evaluation of progesterone (PG) mucoadhesive vaginal tablets.
Part III: Assessment of the In-vivo performance of the selected formulations in the experimental animals, this part is divided into two chapters:
• Chapter I: Bioavailability studies of PG from the selected mucoadhesive vaginal tablets.
• Chapter II: Histological study of endometrium and myometrium in rabbits.