The effect of pH on release of PGE₂ from vaginal and endocervical preparations for induction of labour: an in‐vitro study

Abstract

Objective To study the effect of pH and precoating with obstetric cream on the release of prostaglandin E2 (PGE2) from commercially available triacetin and starch based gels, lactose based vaginal tables and sustained release hydrogel polymer pessaries in‐vitro. Design A prospective observational study. Methods PGE2 preparations held in dialysis bags were placed in Ringers lactate buffer and release of PGE2 into the buffer was measured over 8–12 h by radio‐immunoassay. The hydrogel polymer pessary was also assessed after precoating with obstetric cream. Main outcome measures In‐vitro PGE2 release at pH 7.4, pH 5.4 and pH 3.4. Results The gel preparations provided rapid and reliable release, while the lactose based vaginal tablet provided much lower release of PGE2 with sudden and variable release occurring after 5–8 h, an effect which was enhanced at low pH. With the triacetin gel preparation, release of PGE2 was reduced at lower pH, while the starch based gel appeared to provide optimal release at pH 5.4. The hydrogel polymer pessaries provided linear release in‐vitro and this was reduced at pH 3.4. In addition, precoating the sustained release hydrogel polymer pessaries with obstetric cream virtually abolished release of PGE2. Conclusions As the vagina is normally acid, these results suggest that vaginal pH could influence PGE2 release and this may result in variable clinical responses. In view of this, pH should be taken into account in the development of preparations for clinical use. Furthermore, the use of obstetric cream should be avoided when administering PGE2 preparations for induction of labour.

Effect of vaginal pH on efficacy of dinoprostone gel for labour induction

“…(6.5 to 7.5) It was also reported in the two in vitro studies that along with the increased release of PGE 2 , it is also predominantly ionized at a pH of 7.5 (pKa, 4.9), which diminishes the potential of its systemic absorption. 13,16 Lyrenas et al further noted that high vaginal pH (6.5-7.5) and therefore increased PGE 2 release did not equate to increased plasma concentrations of PGE 2 and its metabolites. Therefore, why vaginal pH affected the cervical priming but did not affect the labor outcomes in present study may be due to these findings that ionization of PGE 2 in high pH might cause local effects, like change in Bishop's score, and the diminishing of its absorption may decrease its systemic effects and therefore, absence of change in labor outcome.…”

“…There are studies that mention that pH may change the degree of ionization of a drug and affect the absorption of the drug resulting in variable clinical responses. 13,16 Vaginal pH changes also has a role in preterm delivery which suggests that it has a role in influencing cervical ripening. 14,15 The purpose of this study is to evaluate the influence of vaginal pH on the efficacy of PGE 2 gel for cervical ripening/labour induction which would improve patient selection for PGE 2 induction and reduce the incidence of failed induction with PGE 2 .…”

Comparaison de deux régimes d’administration intracervicale de Prépidil® dans le déclenchement artificiel du travail à terme : essai prospectif randomisé

“…Ce dernier paramètre a été mesuré afin d'éviter tout biais de sélection dans les deux groupes, en effet plusieurs travaux publiés dans la littérature ont souligné l'existence d'une corréla-tion entre le pH vaginal et l'absorption et modulation de l'activité des prostaglandines locales et donc tous les indices de progression de la maturation cervicale [12,13].…”

Advanced topical drug delivery system for the management of vaginal candidiasis

“…Thick mucus is less permeable and vice versa. It act as permeability barrier for most of the drugs (Johnson et al, 1992). It can be exploited for bioadhesive delivery systems For pH-sensitive drugs and drugs which are weak electrolyte, alteration in vaginal pH may alter drug ionization, solubility, stability and subsequent drug release (Katz & Dunmire, 1993 (Robinson & Bologna, 1994).…”