Preparation and evaluation of vaginal suppo-sponges loaded with benzydamine, in-vitro/in-vivo study.

This study aimed to design a new Benzydamine HCl (BNZ) suppo-sponge for controlled, mucoadhesive dosage form for vaginal candidiasis treatment, offering advantages over traditional creams, ointments, or gels. BNZ-loaded suppo-sponges were fabricated by simple casting / freeze-drying technique utilizing the cross-linking of chitosan (Cs) with vanillin (V). Vaginal suppo-sponges were prepared based on different vanillin cross-linking ratios (V).n), from 0 to 2%w/w. To best of our knowledge, this is the first study that uses Schiff's base between chitosan and vanillin as a drug delivery system to treat fungal vaginal infections. Schiff's base formation was confirmed by FT-IR. In-vitro appraisal showed acceptable physical and mechanical characteristics. Formulations based on cross-linking of Cs with V showed a more pronounced in-vitro antifungal activity. In-vitro drug release revealed a prolonged release pattern, becoming more noticeable with the higher cross-linked suppo-sponges (22.34% after 8 h). In-vivo testing of CsV2 suppo-sponge indicated a more pronounced reduction in fungal count than both CsV0 and Tantum® Rosa in the first week, with a peak reduction on day 7 and the 10th and 11th days of the second week. Conclusively, Chitosan/vanillin suppo-sponges represent a promising delivery system for drugs intended for local treatment of vaginal candidiasis. than both CsV0 and Tantum® Rosa in the first week, with a peak reduction on day 7 and the 10th and 11th days of the second week. Conclusively, Chitosan/vanillin suppo-sponges represent a promising delivery system for drugs intended for local treatment of vaginal candidiasis.

Pentoxifylline/Valsartan co-delivery in liposomal gel alters the inflammatory HMGB-1/ TLR pathway and promotes faster healing in burn wounds: A promising repurposed approach.

Burn wounds are one of the most severe complex forms of trauma. Hence, new treatment strategies that facilitate the healing process; reduce the severity and the healing time is the main concern of the health care systems. In this work, pentoxifylline-valsartan, (PTX- VAL), loaded liposomes integrated into gel were designed for the first time as a novel co-delivery carrier for the treatment of burn wounds. The objective of this work was to investigate the ability of the nano-based liposomal system to co-entrap two repurposed drugs; hydrophilic pentoxifylline and lipophilic valsartan for topical treatment of burn wounds. The impact of increasing the phospholipid amount to enhance the co-entrapment of PTX and VAL was investigated and in-vitro evaluation of the prepared formulations was conducted to choose the optimum composition with the highest entrapment of both drugs adopting a simple, reliable derivative spectrophotometric method. Structure elucidation was also performed using a transmission electron microscope. In addition, A simple selected derivative spectrophotometric method was developed for the assay of PTX-VAL novel combination. The proven selectivity, precision and accuracy assured the reliability of this analytical method. Being economic and fast makes routine application of the developed analytical method is recommended in pharmaceutical industry. The selected liposomal formulation integrated into gel matrix (PTX-VAL-LG) showed; nanometric size, acceptable entrapment efficiency of both PTX and VAL as well as sustained release profiles and thus, enhanced action.

Valsartan solid lipid nanoparticles integrated hydrogel: A challenging repurposed use in the treatment of diabetic foot ulcer, in-vitro/in-vivo experimental study.

The article presents an experimental study on the possible repurposed use of valsartan (Val), in the local treatment of uncontrolled diabetic foot ulcer. Solid lipid nanoparticles (SLN), loaded with Val were prepared by applying 32 full factorial design using modified high shear homogenization method. The lipid phase composed of Precirol® ATO 5 (P ATO 5) and/or Gelucire 50/13 (G 50/13) in different ratios and a nonionic emulsifier, Pluronic 188 (P188), was used in different percentages. Optimized formulation was further integrated in hydroxyl propyl methyl cellulose (HPMC) gel for the ease of administration. In-vitro and in-vivo characterizations were investigated. The prepared nanoparticles showed small particle size, high entrapment efficiency and sustained drug release. Microbiologically, Val-SLN showed a prominent decrease in the biofilm mass formation for both gram-positive and gram-negative bacteria, as well as a comparable minimum inhibitory concentration level to levofloxacin alone. Diabetes was induced in 32 neonatal Sprague-Dawley rats. At 8 weeks of age, rats with blood sugar level >160 were subjected to surgically induced ulcer. Treatment with Val-SLN for 12 days revealed enhanced healing characteristics through cyclooxygenase-2 (COX-2), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), nitric oxide (NO), transforming growth factor-beta (TGF-ß), matrix metalloproteinase (MMPs) and vascular endothelial growth factor (VEGF) pathways. Histological examination revealed re-epithelization in Val-SLN treated ulcer, as well as decrease in collagen using trichrome histomorphometric analysis.

Eco-Friendly Tadalafil Surfactant-Free Dry Emulsion Tablets (SFDETs) Stabilized by In Situ Self-Assembled Aggregates of Natural Oil and Native Cyclodextrins.

The main principles of green chemistry and engineering were extended to pharmaceutical formulations to prepare eco-friendly surfactant-free dry emulsion tablets (SFDETs) devoid of solvents or synthetic surfactants. Surfactant-free emulsions were stabilized by in situ cyclodextrins/sweet almond oil inclusion complexes and assessed for creaming stability. Formulation variables' effects on the emulsion droplet size and tadalafil solubility were studied using 22 × 3 factorial design. The emulsions exhibited nanometric and micrometric droplet sizes. The optimized nanoemulsion was loaded with tadalafil, morphologically evaluated, and utilized for preparing lyophilized SFDETs using different gelatin/Pearlitol® ratios. The tablets were characterized and the selected formulation was subjected to storage for 6 months. The emulsions prepared using ß-cyclodextrin or higher concentrations of α-cyclodextrin showed little or no phase separation. Statistical analysis revealed significant influence of cyclodextrin type and amount on droplet size, while cyclodextrin type and oil volume exhibited significant effect on drug solubility. Morphological examination revealed non-aggregated spherical emulsion droplets. The prepared tablets showed satisfactory mechanical strength, short disintegration times, and enhanced drug dissolution. The selected tablet formulation (gelatin/Pearlitol®, 4:2 w/w) showed acceptable stability at 25°C/60% relative humidity. An overall conclusion claims that the absence of surfactants is expected to minimize the proposed tablets' in vivo toxicity and environmental concerns.

Controlled release Ibu-cryobarriers for the prevention of post-operative adhesions: In-vitro/in-vivo comparative study.

Post-operative adhesion is a common cause of several complications including intestinal obstruction, chronic pelvic pain and/or infertility. Adhesions are fibrous bands that result from the inflammatory reactions due to peritoneum damage. The current study focused on designing an effective anti-inflammatory loaded barrier for the prevention of post-operative adhesions. The proposed method is based on the use of polyvinyl alcohol (PVA), cryobarrier loaded with Ibuprofen (Ibu). Anti-adhesive Ibu-cryobarriers were prepared in different forms, and subjected to in-vitro evaluation comprising; drug release rate, maximum swelling index, morphological examination using scanning electron microscope (SEM), fourier-transform infrared spectroscopy (FTIR) and mechanical properties. Optimized cryobarriers were further investigated for their in-vivo effectiveness in preventing post-operative adhesions in female Sprague-Dawley rats. All formulations showed appropriate physical and morphological characteristics, in-vitro controlled sustained drug release profiles during a period of seven days with acceptable maximum swelling index. Invivo, all cryobarriers were equivalent to each other concerning serum or tissue parameter. However, morphological and histopathological evaluations revealed that both xerocryogel and lyophilized cryofilms are more effective than the cryogel in prevention of post-operative peritoneal adhesions. The current study showed the possibility of preparing drug loaded cryobarriers using simple technique with an effective in vivo post-operative adhesion prevention.

Novel levocetirizine HCl tablets with enhanced palatability: synergistic effect of combining taste modifiers and effervescence technique.

OBJECTIVES: Levocetirizine HCl, a second-generation piperazine derivative and H1-selective antihistaminic agent, possesses few side effects. The first objective of the study was to compare and evaluate the taste-masking effect of different ratios of 2-hydroxypropyl-ß-cyclodextrin and mannitol on levocetirizine HCl using an inclusion complex and solid dispersion, respectively. The second objective was to study the possibility of preparing and evaluating effervescent tablets from the best-chosen taste-masked blends for the purpose of their use either as orodispersible tablets or as water-soluble effervescent tablets, according to patients' will. MATERIALS AND METHODS: Prepared taste-masked blends were prepared and subjected to palatability, Fourier-transform infrared spectroscopy, and differential scanning calorimetry studies. Tablets containing different percentages of effervescent mixtures were prepared by direct compression on the selected taste-modified blends. Evaluation tests were conducted, including flowability and compressibility on the precompressed blends and hardness, friability, wetting time, effervescent time, in vitro, in vivo disintegration time, and in vitro dissolution study on the compressed tablets. Formulated tablets were evaluated and compared to marketed orodispersible tablets for mouth feel and palatability. RESULTS: All prepared tablets showed convenient physical and palatability properties compared to the selected brand. The in vitro drug-release study revealed fast release of levocetirizine HCl within 5 minutes from all prepared tablets. CONCLUSION: Levocetirizine HCl effervescent tablets are likely to increase patient compliance with drug administration. Moreover, the use of these effervescent tablets in an orodispersible dosage form can improve oral drug bioavailability and act as an attractive pediatric dosage form.

Innovation of natural essential oil-loaded Orabase for local treatment of oral candidiasis.

PURPOSE: Oral candidiasis may be manifested in the oral cavity as either mild or severe oral fungal infection. This infection results from the overgrowth of Candida species normally existing in the oral cavity in minute amounts based on many predisposing factors. Several aspects have spurred the search for new strategies in the treatment of oral candidiasis, among which are the limited numbers of new antifungal drugs developed in recent years. Previous studies have shown that thyme and clove oils have antimycotic activities and have suggested their incorporation into pharmaceutical preparations. This study aimed to investigate the possibility of the incorporation and characterization of essential oils or their extracted active ingredients in Orabase formulations. METHODS: Orabase loaded with clove oil, thyme oil, eugenol, and thymol were prepared and evaluated for their antifungal activities, pH, viscosity, erosion and water uptake characteristics, mechanical properties, in vitro release behavior, and ex vivo mucoadhesion properties. RESULTS: All prepared bases showed considerable antifungal activity and acceptable physical characteristics. The release pattern from loaded bases was considerably slow for all oils and active ingredients. All bases showed appreciable adhesion in the in vitro and ex vivo studies. CONCLUSION: The incorporation of essential oils in Orabase could help in future drug delivery design, with promising outcomes on patients' well-being.

Design and formulation of a topical hydrogel integrating lemongrass-loaded nanosponges with an enhanced antifungal effect: in vitro/in vivo evaluation.

Lemongrass oil (LGO) is a volatile oil extracted from the leaves of Cymbopogon citratus that has become one of the most important natural oils in the pharmaceutical industry because of its diverse pharmacologic and clinical effects. However, LGO suffers from low aqueous solubility, which could lead to a reduced effect. Moreover, the instability of its major active constituent, citral, could lead to volatilization, reaction with other formulation ingredients, and consequently, skin irritation. To surmount these problems, this research aims to formulate lemongrass-loaded ethyl cellulose nanosponges with a topical hydrogel with an enhanced antifungal effect and decreased irritation. The minimal inhibitory concentration and minimal fungicidal concentration of LGO against Candida albicans strain ATC 100231, determined using the broth macrodilution method, were found to be 2 and 8 µL/mL, respectively. The emulsion solvent evaporation technique was used for the preparation of the nanosponges. The nanosponge dispersions were then integrated into carbopol hydrogels (0.4%). Nine formulations were prepared based on a 32 full factorial design employing the ethyl cellulose:polyvinyl alcohol ratio and stirring rate as independent variables. The prepared formulations were evaluated for particle size, citral content, and in vitro release. Results revealed that all the nanosponge dispersions were nanosized, with satisfactory citral content and sustained release profiles. Statistical analysis revealed that both ethyl cellulose:polyvinyl alcohol ratio and stirring rate have significant effects on particle size and percentage released after 6 hours; however, the effect of the stirring rate was more prominent on both responses. The selected hydrogel formulation, F9, was subjected to surface morphological investigations, using scanning and transmission electron microscopy, where results showed that the nanosponges possess a spherical uniform shape with a spongy structure, the integrity of which was not affected by integration into the hydrogel. Furthermore, the selected formulation, F9, was tested for skin irritation and antifungal activity against C. albicans, where results confirmed the nonirritancy and the effective antifungal activity of the prepared hydrogel.

Osteogenic effect of locally applied Pentoxyfilline gel: in vitro and in vivo evaluations.

The aim of this study was to formulate Pentoxyfylline drug (PTX) as a local bioadhesive Carbopol (Cbp) based gels for the aid of bone induction around an endosseus oral implant. The local delivery of the drug will probably avoid most of the problems associated with its systemic use including; disturbances in gastrointestinal tract and the central nervous system. Two concentrations of 1% and 3% Cbp containing 1% PTX were prepared. The gels were investigated for their physicochemical properties. Cbp based gels were found to be translucent with good homogeneity, uniform distribution of the drug and absence of any lumps. The pH of the gels was within neutrality, 7.1, which is considered to be acceptable to avoid the risk of any possible irritation in the oral cavity. The Cbp gels exhibited satisfactory bioadhesive properties and a pseudo-plastic rheological behavior. Cumulative drug released from the gels showed a controlled-release for more than 24 hours with the order of 3% >1% and the drug was released by diffusion mechanism from both gels. Statistical analysis revealed non-significant difference in drug content, rheological property and release rate of the stored gels for six months compared to the fresh ones. In vivo experimental results in rabbits have shown significant difference in bone depth induction of 3% and 1% Cbp gels with the formation of strong organized bone over the control group. Local administration of Pentoxifylline could be regarded as a valid approach in the management of osseointegration.

Metronidazole and Pentoxifylline films for the local treatment of chronic periodontal pockets: preparation, in vitro evaluation and clinical assessment.

OBJECTIVE: Periodontitis is one of the most important chronic inflammatory dental diseases arising from the destructive actions caused by a variety of pathogenic organisms presented in the oral cavity. The aim of this study is the preparation and in vitro evaluation of films for the local treatment of periodontal pockets. METHODS: The prepared films contained either metronidazole (Mtr), for its antimicrobial effect in periodontal diseases, using a mixture of polymers namely hydroxypropyl methyl cellulose, Carbopol 934 or locally applied Pentoxifylline (PTX), for its anti-inflammatory activity, using chitosan. All films were prepared using solvent casting technique and were evaluated for their physical characteristics, drug content uniformity, surface pH, swelling behavior, mechanical properties and in vitro release. Further characterization was done on the selected formulations using differential scanning calorimetry and scanning electron microscopy for surface structure. Clinical evaluation tests were also performed. RESULT: Appropriate physical characteristics and mechanical properties for most formulations and their suitability for periodontal application were observed. In vitro drug release from most films showed a burst release rate for both Mtr and PTX during the first 2 h after which the release rate was markedly decreased. Clinical trials on patients revealed the advantageous use of Mtr and PTX as an adjunct treatment with traditionally used dental techniques. CONCLUSION: The effectiveness of the co-therapy of either drug could add benefit in the eradication of chronic periodontal hazards.

Antihyperglycemic activities of extracts of the mistletoes Plicosepalus acaciae and P. curviflorus in comparison to their solid lipid nanoparticle suspension formulations.

The antihyperglycemic activity of the extracts and preparations of solid lipid nanoparticle suspensions of two mistletoes growing in Saudi Arabia, Plicosepalus acaciae and P. curviflorus, as well as their possible antioxidant effect were investigated in a type 2 diabetic animal model. Type 2 diabetes was induced in adult male Wistar rats by a high-fat diet followed by injection of streptozotocin (STZ). The diabetic rats were treated in parallel with pioglitazone hydrochloride (PIO), non-toxic extracts of P. acaciae and P. curviflorus, as well as three different solid lipid nanoparticle (SLN) suspension formulations prepared from each of the two extracts. Blood glucose level, insulin resistance, oxidative stress parameters, and antioxidant markers were determined. The total extracts of P. acaciae and P. curviflorus as well as the SLN formulations exhibited a significant blood glucose-lowering effect associated with antioxidant effects in the diabetic rats. The SLN preparation with the highest lipid content gave the best result. Reduction of hyperglycemia and insulin resistance in the diabetic rats was, at least partly, due to the antioxidant activities of the extracts and their SLN formulations.