The effect of the source and the concentration of polymers on the release of chlorhexidine from mucoadhesive buccal tablets.

In the current work, two groups of chlorhexidine mucoadhesive buccal tablets were prepared, using either rod or irregularly-shaped spherical particles of hydroxypropyl methylcellulose and different ratios of poloxamer 407 (P407). The tablets were designed to release the drug over two hours. Their physicochemical properties and drug release profiles were investigated. The impact on dry granulation, the ex-vivo mucoadhesion, the swelling index, the morphology of swollen tablets and the drug release kinetic were investigated. Drug-polymers chemical interaction was studied using Fourier Transforms Infrared Spectroscopy (FTIR) and differential scanning calorimetry (DSC). Due to different particle shapes, the preparation of dry granules required a 40 KN force for rod-shaped particles compared to 10 KN for the irregularly-shaped spherical particles. All formulations showed at least two-hours residence time using ex-vivo mucoadhesion. Statistically, there was no significant difference in the swelling index, drug release nor its kinetic for both groups. However, the microscopical morphology of the swollen tablet and the size of the pores were affected by particle shape. Increasing the ratio of P407 to 62.5% resulted in a pronounced increase in drug release from around 60% to >90% after two hours. Following the FTIR and DSC analyses, no chemical interaction was noted apart from the steric hindrance effect of P407, which was observed even with the physical mixtures.

Fast and pH-dependent release of domperidone from orally disintegrating tablets.

There has been growing interest in orally disintegrating tablets (ODTs) during the last decade due to their better patient acceptance and compliance. Further, drug dissolution and absorption may be significantly improved. This work describes the preparation of fast and pH-dependent release ODTs for domperidone by direct compression using crospovidone as superdisintegrant. Solid dispersions of domperidone and Eudragit L100-55, at different weight ratios, were prepared and characterized by DSC, TGA, X-ray diffraction, and FTIR, which indicated the presence of drug-polymer interaction. Disintegration time, friability, and hardness of ODTs were evaluated. In vitro drug release in 0.1N HCl and in phosphate buffer (pH 5.8 and 6.8) was investigated. All domperidone ODTs had fast disintegration times (6 KP) and acceptable friability (<1%). Drug release from fast release ODTs was highly improved; reaching 97% after 10 min in 0.1N HCl, compared to the dissolution of the free drug. Drug release from solid dispersions was pH dependent; showing higher release rates at pH 6.8 than at lower pH values. The controlled-release ODT resulted in 47% drug release in 0.1N HCl, with the rest of drug released at pH 6.8. Domperidone ODTs were considered suitable for ODT formulation.

Cytotoxic Activity of Hypericum triquetrifolium Turra Methanolic Extract Against Cancer Cell Lines.

BACKGROUND: Since ancient times, several people in the Mediterranean region have employed Hypericum triquetrifolium Turra in traditional medicine. However, only the composition of its essential oils has received extensive research. OBJECTIVE: This study investigated the cytogenetic and cytotoxic effects of H. triquetrifolium methanolic leaf extract on four different cancer cell lines. METHODS: Methanolic extract of H. triquetrifolium leaves was prepared. Albino male mice were grouped into five: group 1 (blank control) received water;group II (CYP) received cyclophosphoamide; groups III, IV, and V were administered 50, 100, and 200 mg/kg of H. triquetrifolium extracts. On the 11th day, the animals were sacrificed and bone marrowwascollected. The metaphase index (MI) of the bone marrow cells was determined to evaluate the cytogenetic effect of the extract. The cytotoxic activity of the extract was tested on four cancer cell lines (HepG2, PC3, MDA, and A594), while WRL-68 normal cells were employed as control. RESULTS: The index of bone marrow cells in cyclophosphamide (CYP)-treated albino male mice shows a significant difference (P ≤ 0.05) between concentration inhibition 50 % IC50 of cancer cell line compered to WRL-68 normal cells, on MDA and WRL-68 cells (IC50 =185.7, 200.7), HepG2 and WRL-68 (IC50 104.9, 564.6), A549 and WRL-68 (IC50 115, 192), PC3 and WRL-68 (IC50 160.7, 298.7). The results showed that the extracts was able to increase metaphase index compared to cyclophasoamide-treated mice, which caused a drop in the percentage of metaphase index. CONCLUSIONS: The current study was showed that significant anti - proliferation activity of Hypericum triquetrifolium methanolic extract against MDA-MB-231 cell line is an epithelial, human breast cancer cell line,WRL-68, HepG2 and lung cancer cell lines (A594).

The Investigation of Thymol Formulations Containing Poloxamer 407 and Hydroxypropyl Methylcellulose to Inhibit Candida Biofilm Formation and Demonstrate Improved Bio-Compatibility.

The aim of this study was to investigate the potential of thymol to inhibit Candida biofilm formation and improve thymol biocompatibility in the presence of hydroxypropyl methylcellulose (HPMC) and poloxamer 407 (P407), as possible drug carriers. Thymol with and without polymers were tested for its ability to inhibit biofilm formation, its effect on the viability of biofilm and biocompatibility studies were performed on HEK 293 (human embryonic kidney) cells. Thymol showed a concentration dependent biofilm inhibition; this effect was slightly improved when it was combined with HPMC. The Thymol-P407 combination completely inhibited the formation of biofilm and the antibiofilm effect of thymol decreased as the maturation of Candida biofilms increased. The effect of thymol on HEK 293 cells was a loss of nearly 100% in their viability at a concentration of 250 mg/L. However, in the presence of P407, the viability was 25% and 85% using neutral red uptake and sulforhodamine B assays, respectively. While, HPMC had less effect on thymol activity the thymol-P407 combination showed a superior inhibitory effect on biofilm formation and better biocompatibility with human cell lines. The combination demonstrates a potential medical use for the prevention of Candida biofilm formation.

The Activity of PHMB and Other Guanidino Containing Compounds against Acanthamoeba and Other Ocular Pathogens.

In recent years, a rise in the number of contact lens users in the UK and worldwide coincided with an increased incidence of microbial keratitis. The aim of this study was to investigate the antimicrobial activities of polyhexamethylene guanidine (PHMG), polyaminopropyl biguanide (PAPB), and guazatine in comparison to the common contact lens disinfectant constituent, polyhexamethylene biguanide (PHMB). The study investigated these compounds against a broad range of organisms, including Acanthamoeba castellanii, Acanthamoeba polyphaga, Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans. This study demonstrated that PHMG, PAPB, and guazatine are equal in activity to PHMB against Acanthamoeba trophozoites and cysts. PHMG and PAPB are also equal in activity to PHMB against S. aureus and P. aeruginosa, whereas PHMG shows significantly better activity than PHMB against C. albicans (p < 0.001). To our knowledge, this is the first study to demonstrate the effectiveness of PHMB, PHMG, PAPB, and guazatine against Acanthamoeba and other ocular pathogens. As alternatives to PHMB, these compounds warrant further investigation for inclusion in contact lens solutions and for the treatment of keratitis.

Chlorhexidine Mucoadhesive Buccal Tablets: The Impact of Formulation Design on Drug Delivery and Release Kinetics Using Conventional and Novel Dissolution Methods.

Oropharyngeal candidiasis (OPC) is a mucosal infection caused by Candida spp., and it is common among the immunocompromised. This condition is mainly treated using oral antifungals. Chlorhexidine (CHD) is a fungicidal and is available as a mouth wash and oral gel. It is used as an adjuvant in the treatment of OPC due to the low residence time of the current formulations. In this study, its activity was tested against C. albicans biofilm and biocompatibility with the HEK293 human cell line. Then, it was formulated as mucoadhesive hydrogel buccal tablets to extend its activity. Different ratios of hydroxypropyl methylcellulose (HPMC), poloxamer 407 (P407), and three different types of polyols were used to prepare the tablets, which were then investigated for their physicochemical properties, ex vivo mucoadhesion, drug release profiles, and the kinetics of drug release. The release was performed using Apparatus I and a controlled flow rate (CFR) method. The results show that CHD is biocompatible and effective against Candida biofilm at a concentration of 20 µg/mL. No drug excipient interaction was observed through differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR). The increase in P407 and polyol ratios showed a decrease in the swelling index and an increase in CHD in vitro release. The release of CHD from the selected formulations was 86-92%. The results suggest that chlorhexidine tablets are a possible candidate for the treatment of oropharyngeal candidiasis.

Mechanical performance of additively manufactured pure silver antibacterial bone scaffolds.

Implant infection is a serious complication resulting in pain, mortality, prolonged recovery, and antimicrobial resistance (AMR). Reducing the risk-of-infection associated with tissue implants require imminent attention, where pure silver (Ag) offers enormous potential. However, the printability, mechanical performance nor microbial resistance of additively manufactured (AM) pure Ag is unavailable in literature. This is critical as Ag is thought to play a vital role in the development of AM patient-specific infection resistant implants in the decade to come. The study therefore additively manufactured 99.9% pure-Ag through selective laser melting (SLM) and systematically investigates its mechanical performance. The validated SLM process parameters were then used to conceive two fully porous bone scaffold each at approximately 68 and 90% (wt.) porosity. While the study brings to attention the potential defects in SLM pure-Ag through X-ray nanotomography (X-ray nCT), the mechanical properties of porous Ag scaffolds were found to be similar to cancellous bone. The study achieved the highest SLM pure-Ag density of 97% with Young's modulus (E), elastic limit (σe), yield strength (σy), ultimate strength (σult) and ultimate strain (εult) in the range of 15.5-17.8 GPa, 50.7-57.7 MPa, 57.6-67.2 MPa, 82.4-95.9 MPa and 0.07-0.10 respectively. The antimicrobial efficacy of printed silver was tested against the common implant infection-causing Staphylococcus aureus and led to 90% and 99.9% kill in 4 and 14 h respectively. The study, therefore, is a first step towards achieving a new generation Ag-based AM infection resistant porous implants.