Pharmaceutical Manufacturing Handbook: Production and

824 VAGINAL DRUG DELIVERY
distribution and drug release can infl uence the fi nal performance of the formulation,
being preferable to use specifi cally vaginal designed drug delivery systems, or at
least study the pharmacokinetics of oral tablets after vaginal administration [82] .
Capsules, particularly soft capsules, have been used as vaginal drug delivery
systems, but with modest popularity. These systems are relatively stable, particularly
when compared with semisolid formulations or vaginal suppositories, being an
adequate way to deliver liquid drugs within a solid dosage form.
Vaginal suppositories, also referred as ovules or pessaries, are ovoid - shaped, solid
(but generally malleable) dosage forms specifi cally designed for vaginal administration.
These systems usually weigh 2 – 3 g, although formulations with up to 16 g have
been used in the past [83] . Vaginal suppositories have a long history of use as vaginal
drug delivery systems, mainly in the management of local conditions. Major advantages
are their reduced price and ease of manufacture. However, they present some
inconveniences, such as messiness, low retention in the vagina, and poor stability,
the last feature due to their temperature and moisture sensibility.
Vaginal suppositories are very close to rectal suppositories in terms of excipient
nature and manufacturing process. Thus, they are usually prepared by fusion of the
excipient(s) (referred as “ base ” ) and incorporation of the active substance(s), this
mixture being subsequently poured into molds and allowed to solidify. Other
methods, such as by compression, can also be used. Several substances have been
utilized as bases for the formulation of vaginal suppositories: gelatin and glycerin,
cocoa butter, semisynthetic glycerides, and polyethylene glycol, among others [83] .
Composition of vaginal suppositories is importantly related to their melting or dissolution,
thus infl uencing drug release profi le. Generally, it can be stated that drug
release rate increases as the melting temperature of a suppository decreases or as
its dissolution time in vaginal fl uids increases. Also, affi nity of the drug for the base
infl uences its release from vaginal suppositories: Greater release of drug is expected
when there is less affi nity between the active substance(s) and the base [84] . The
melting temperature and melting process of vaginal suppositories can be characterized
by several techniques, such as differential scanning calorimetry and viscosity
and dilatometry methods, among others [85] . Specifi c pharmaceutical characterization
of vaginal suppositories includes the determination of disintegration time and
breaking hardness. Also, other standard quality control tests include appearance
description, surface texture evaluation, pH determination, uniformity of content,
and microbial limit testing [86, 87] .
Recently, sustained - release vaginal suppositories have been developed in order
to attain drug delivery systems with improved performance. Sustained release can
reduce the number of administrations, thus improving patient compliance. A base
composition consisting of a polymeric gum (carboxymethylcellulose and xanthan
gum), a dispersing agent (colloidal silicone dioxide), and polyethylene glycol,
referred as long acting, sustained release of spermicide (LASRS), has recently been
studied by Zaneveld et al. in order to deliver contraceptives and microbicides [88] .
Results showed that a LASRS base is able to spread quickly and evenly over the
mucosa, being retained in place for prolonged periods of time and allowing long -
lasting effi cacy for several active drugs. Preliminary human trials have confi rmed
these results [89] . In another study, Mandal developed hydrophilic vaginal suppositories
comprising mixtures of miconazole cross - linked with poly(vinyl alcohol) by