Formylation &Evaluation of certain Antihyprtensive Drugs Administertered Rectally

• Formulation of drugs in rectal dosage forms may considered to be a possible way to solve problems associated with other dosage forms and to achieve sustained drug release. The rectal route is useful for the treatment of either local or systemic diseases overcoming some drawbacks of conventional administration routes.• Rectal route of administration has several advantages as it is available for patients who can not swallow tablets or capsules, it is ideal dosage form for infants, children and patients with nausea, vomiting, avoid gastric irritation and hepatic first pass metabolism.• Natural and synthetic drugs were formulated in the form of suppositories to produce systemic effects. Moreover, suppositories could be useful if formulated as sustained release dosage form for the treatment of chronic diseases such as hypertension and asthma.• It is considered a convenient route of drug administration specially in cardiovascular emergencies where the patient is unconscious and oral route and sometimes parentral route are not possible.• Certain antihypertensive drugs such as Atenolol and Diltiazem HCL possess short half life and decreased bioavailability. The aim of the present thesis is to formulate these two drugs in the form of rectal suppositories to solve the previously mentioned problems.• This thesis is divided into two parts, each consist of two chapters.Part oneFormulation and Evaluation of Atenolol SuppositoriesThe work in this part is divided into two chapters:Chapter (1): Formulation and In-Vitro Evaluation of Atenolol Conventional and Modified Release Suppositories.(1) In this chapter, suppositories were prepared by direct fusion method, each containing 100 mg Atenolol. They were prepared using either hyDROPhilic bases such as poly ethylene glycol (PEG) and glycerinated gelatin (G.G), or hyDROPhobic bases such as cocoa butter (C.B) or hyDROPhobic emulsifying bases such as witepsol H15 (WH15) suppocire NA50 (S NA50).(2) Interestingly, Atenolol showed high release rate from both hyDROPhilic and hyDROPhobic bases except for C.B. Atenolol release from cocoa butter suppositories was slightly enhanced by incorporation of different types and concentrations of surfactants, namely Tween 80 (T80), Tween 20 (T20) and Brij 92 (B92).(3) On the other hand, hydroxypropyl methyl cellulose (HPMC) or mixture of span 60 (Sp 60) and cholesterol (CH) were used as release modifiers for Atenolol from PEG and WH15 bases which released the drug very rapidly in order to get sustained release (SR) suppositories. Suppository formulations containing Sp60/CH as 50% of the base weight can be considered as new suppository formulae of proniosomal type in case of PEG bases or emulsifying type when WH15 base was used.SR suppositories were formulated in this study using different strategies; the first one was to use HPMC as viscosity mod Fraxius ercelsior L. was reported to have mild diuretic , purgative, antipyrelic and analgesic action, while the use of its decoction externally in form of compresses was valuable for treatment of certain suppurating cuts and sores.An infusion made from the bark of Fraxinus Americana L. has a febrifuge effect and astringent action.