Development and Evaluation of Vaginal Suppository Containing Althaea officinalis L. Polysaccharide Extract

Abstract

Intrauterine adhesions cause several gynecological problems. Althaea officinalis L. roots known as marshmallows contain polysaccharides (M.P.) which possess anti-inflammatory and anti-ulcerogenic activities also can form a bio-adhesive layer on damaged epithelial membranes prompting healing processes. Vaginal formulations of herbal origin are commonly applied to relieve cervico-uterine inflammation. Herein, we aim to develop and evaluate vaginal suppositories containing polysaccharides isolated from the A. officinalis root. Six formulations (four P.E.G.-based and two lipid-based suppositories containing 25% and 50% M.P.) met standard requirements, which were then subjected to qualitative and quantitative evaluation. All suppositories exhibited acceptable weights, hardness, content uniformity, melting point, and disintegration time, which fall within the acceptable recommended limits. Higher concentrations of M.P. in PEG-bases moderately increased the hardness (p<0.05). PEG-formulations showed content uniformity>90% of the average content while it was 75-83% for suppocire formulations. All formulations disintegrated in<30minutes. In-vitro release test revealed that M.P. release from 25%-MP formulations was higher than that of 50%-M.P. suppositories. Overall, results revealed the feasibility of preparing P.E.G.-or lipid-based suppositories containing M.P., which met the B.P. quality requirement.

Introduction

Asherman’s Syndrome is a condition that is characterized by intrauterine adhesions (I.U.A.), causing several symptoms, including pelvic pain, menstrual anomalies, infertility, miscarriage, and related psychological symptoms (Santamaria, Isaacson, Simón, 2018). The gold standard for I.U.A. treatment would be hysteroscopic lysis of adhesions through surgery. However, recurrence occurs frequently (Salazar, Isaacson, Morris, 2017), and prevention methods including pharmacological treatment and physical barriers have a high recurrence rate (Tu et al., 2013).
Althaea officinalis L. (marshmallow) is a perennial plant with erect and woody stems from Malvaceae (Akbar, 2020). Marshmallow roots have been used in several traditional systems of medicine for more than two millennia (Ibn-Sina,1987).

Marshmallow root contains 5-11% water-soluble mucilage polysaccharides composed of galacturonorhamnans, glucans, arabinans, and arabinogalactans carbohydrates (Dawid-Pać, 2013).
Anti-inflammatory, anti-ulcerogenic, and antimicrobial activities have been reported for different parts of A. officinalis (Rezaei et al., 2015; Hage-Sleiman, Mroueh, Daher, 2011; Sleiman, Daher, 2009). Many herbal polysaccharides have been shown to enhance intrinsic antioxidant enzymes, induce apoptosis of cervical cancer HeLa cells and possess immunomodulating effects (Li et al., 2009; Cao et al., 2010; XiaoPing et al., 2009). Marshmallow polysaccharides (M.P.) form a bio-adhesive layer on damaged or irritated epithelial membranes prompting healing processes (Schmidgall, Schnetz, Hensel, 2000). Aqueous extract and polysaccharides of marshmallows can effectively stimulate the physiology of epithelial cells through up-regulating genes associated with cell adhesion proteins, growth regulatory factors, cytokine release, extracellular matrix, and apoptosis. Moreover, through passive mucilaginous, barrier-enhancing effects on connective tissue cells, marshmallow roots can accelerate the healing process (Deters et al., 2010).

The vaginal route represents a reduced drug degradation, circumvention of the hepatic first-pass effect, ease of use, and high permeability to many drugs (Mahjabeen et al., 2018). Vaginal formulations of herbal origin are commonly used in traditional medicine systems to relieve cervico-uterine ulcers, infections, and inflammations. Vaginal suppositories are dosage forms prepared using either fatty bases or water-soluble bases. Suppocire vehicles are complex fat suppository bases containing polyoxylglyceride esters which increase drug solubility and bio-availability. Moreover, Suppocire bases have appropriate solidity, and excellent spreading properties (Regdon et al., 1994) Suppocires are widely used as suitable bases for the formulation of vaginal suppositories (Çaliş, Şumnu, Hincal, 1994; Samy et al., 2000). Polyethylene glycol (P.E.G.), another widely-used polymer in drug delivery systems, has high structure flexibility, biocompatibility, amphiphilicity, and high hydration capacity. Moreover, P.E.G. suppositories permit better miscibility with the mucus, providing fast drug dissolution. Drug release rate decreases with increasing M.W. of P.E.G.s (D’souza, Shegokar, 2016).

M.P. can provide a bio-adhesive layer with anti-inflammatory and wound healing effects in the uterine cavity (Deters et al., 2010). It has been shown that polysaccharides can retard the release of co-administered drugs in suppositories (Uekama et al., 1995). This would benefit suppositories to exert local and regional anti-inflammatory and healing effects, including uterine targeting. Therefore, the mucoadhesive properties of M.P. provide promising candidates for vaginal systems (Valenta, 2005).
We aim to develop and evaluate the vaginal suppositories containing polysaccharides isolated from A. officinalis root in the present study.

Materials

Polyethylene glycol (P.E.G.) 400, P.E.G. 2000, PEG 6000, glycerin, n-hexane, and gelatin were purchased from Merck (Germany). Suppocire AGP^® was gifted from Gattefosse (France).

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Mohammadreza Abbaspour; Hoda Hoseini; Zahra Sobhani; Seyed Ahmad Emami; Bibi Sedigheh Fazly Bazzaz; Behjat Javadi. Development and Evaluation of Vaginal Suppository Containing Althaea officinalis L. Polysaccharide Extract. Brazilian Journal of Pharmaceutical Sciences 
https://doi.org/10.1590/s2175-97902022e20868