Preparation and characterization of bioadhesive controlled-release gels of cidofovir for vaginal delivery

The aim of this study was to develop mucoadhesive and thermosensitive gels for vaginal delivery that would be able to provide a controlled release of the model drug, cidofovir. The study also monitored the drug’s potential antiviral properties. Cidofovir was put into the form of a vaginal gel, using mucoadhesive and thermosensitive polymers such as chitosan, Carbopol 974P, HPMC, and poloxamer 407. The physicopharmaceutical properties and stability of the vaginal gel formulations were evaluated. The gel formulation which was prepared with HPMC K100M exhibited the highest viscosity, as well as maximum adhesiveness, cohesiveness, and mucoadhesion values. The results of antiviral activity studies, which used the bovine herpes virus type 1 virus infection in vitro model using Vero cells, demonstrated the antiherpetic effect of the cidofovir gel containing HPMC K100M, at least under in vitro conditions. The study found that a mucoadhesive vaginal gel containing cidofovir can be a promising and innovative alternative therapeutic system for the treatment of genital herpes simplex virus and human papilloma virus induced infections in women.     

Mucoadhesive poly(vinyl alcohol) hydrogels produced by freezing/thawing processes: Applications in the development of wound healing systems

Ultrapure poly(vinyl alcohol) (PVA) hydrogels were prepared by exposing an aqueous solution of 15 or 20 wt% PVA to repeated cycles of freezing for 6 or 12 h at -20°C and thawing for 2 hours at 25°C. The adhesive characteristics of the PVA gels in contact with a reconstituted mucus surface were quantified using a tensile technique. As the number of freezing/thawing cycles increased, the work of fracture (adhesion) decreased due to the increase in the PVA degree of crystallinity. Crystallinity was determined using differential scanning calorimetry. PVA gels prepared from the 20 wt% solution and exposed to two cycles of freezing/ thawing exhibited the largest work of adhesion. Drug delivery studies were conducted with ketanserin, a wound healing enhancer. Release studies were conducted using PVA samples prepared from a 20-wt% solution that were exposed to two or three freezing cycles for 12 h followed by thawing for 2 h. Results from the release of the drug from the PVA sample exposed to two cycles showed that approximately 80% of the ketanserin was released within 4 h.     

Short-term pharmacokinetic comparison of a novel testosterone buccal system and a testosterone gel in testosterone deficient men

SUMMARY

Objective: The primary objective of the study was to compare the percentage of men with mean serum total T (Cave(0–24)) within normal range during the 24-h pharmacokinetic (PK) sampling period on Days 14 and 15.

Methods: Treatment with a new testosterone (T) buccal system, (Striant), 30mg twice daily was compared to a transdermal gel delivery system, (T-gel) [AndroGel 5?g containing 1% (50?mg) T] daily for 14days in T-deficient men. Safety parameters included laboratory assessments and collection of adverse events. Patients were otherwise healthy T-deficient men with total T?<?8.7 nmol/L (< 2.5?ng/mL).

Results: Twenty-six of the 28 patients enrolled completed the 24-h PK assessment. Of the evaluable patients, 92.3% of T buccal system and 83.3% of T-gel patients had Cave(0–24) within the normal range of 10.4-36.4 nmol/L (3.0–10.5?ng/mL). Mean total T values were not different in the T buccal system group (Cave(0–24) 16.7?±?4.7?nmol/L; 4.8?±?1.4?ng/mL) compared to the T-gel group (Cave(0–24) 15.9?±?4.8?nmol/L; 4.6?±?1.4?ng/mL). All T values returned to baseline levels after the study drug was stopped. Serum LH and FSH levels decreased, and E2 increased as expected following T administration. Differences in DHT concentrations between treatment groups were significant (p?=?0.012) with mean DHT levels on Day 14 of 1.9?±?1.4 nmol/L (0.55?±?0.42?ng/mL) for the T buccal system and 3.2?±?1.3?nmol/L (0.93?±?0.38ng/mL) for T-gel, which was greater than the upper level of normal (2.9?nmol/L; 0.85?ng/mL). Statistically significant differences were seen in the mean T/DHT ratio on Days 14     

Mini-tablets: a contemporary system for oral drug delivery in targeted patient groups

Introduction: Mini-tablets represent a new trend in solid dosage form design, with the main goal of overcoming some therapeutic obstacles such as impaired swallowing and polypharmacy therapy, and also offering some therapeutic benefits such as dose flexibility and combined release patterns. Mini-tablets are a promising patient-friendly drug delivery system.

Areas covered: Mini-tablets are tablets with a diameter ≤ 3 mm produced on conventional tablet presses equipped with multiple tooling. Mini-tablet production is similar to the production of standard tablets but requires excellent powder flow due to the small dies, exact control of process parameters and special caution during tablet press assembly in order to avoid tool damage. Mini-tablets (coated or uncoated and single- or multiple-unit systems) are mainly developed as patient-friendly systems for pediatric and geriatric patients and also for personalized medicine because they offer improved swallowing and flexible dosing, combining various release kinetics, doses and active compounds in only one system. Mini-tablets may also be successfully used as multiple-unit modified release systems (extended release, delayed-colon release, pulsatile and bi-modal release and gastroretentive systems) providing improved drug bioavailability compared with single-unit systems.

Expert opinion: Mini-tablets used as single- or multiple-unit oral dosage forms have enormous potential as a patient-friendly drug delivery system for targeted populations, providing improved swallowing, flexible dosing and a combination of different release patterns and/or different active compounds (decreasing dosing frequency and/or polypharmacy therapy problems). In terms of complete expression of the benefits of mini-tablets over other oral dosage forms on the market, further investigation in formulation possibilities and development of suitable dosing devices is of essential importance.     

Use of a mucoadhesive disk for relief of dry mouth: a randomized, double-masked, controlled crossover study

BackgroundDry mouth is a frequent complaint of adults worldwide. In those who experience dry mouth, therapeutic options include the use of salivary substitutes and sialogogues.MethodsThe authors compared the efficacy and safety of mucoadhesive disks (OraMoist, Axiomedic, Zurich; distributed by Quantum Health, Eugene, Ore.) applied three times daily with those of placebo mucoadhesive disks in a double-masked, randomized, controlled crossover study. The primary end point of interest was within-participant differences in subjective (visual analog scale) ratings of dry mouth according to the New York University Bluestone Mouthfeel Questionnaire. The secondary end point was within-participant differences in salivary flow rates.ResultsTwenty-seven participants completed the single-site study. The results showed no significant difference between the two types of mucoadhesive disks, both of which were associated with a statistically significant improvement in the subjective experience of moistness across the 60-minute period after application and compared with baseline measures after two weeks of use. Furthermore, both disks were associated with a statistically significant improvement in salivary flow rates across the 60-minute period after application and compared with baseline measures after one and two weeks of use. The disks were well tolerated, and participants did not report any adverse events.ConclusionsThe mucoadhesive disks used in this study were safe and provided symptomatic relief from dry mouth.Practice ImplicationsPatients with dry mouth may benefit from this novel delivery system.     

Extended Nasal Residence Time of Lysostaphin and an Anti-Staphylococcal Monoclonal Antibody by Delivery in Semisolid or Polymeric Carriers

PURPOSE: Eradication of Staphylococcus aureus nasal colonization reduces the risk of nosocomial and community acquired infections with this organism. This study describes the formulation and use of lysostaphin and BSYX-A110, an anti-lipoteichoic acid monoclonal antibody, for eradication of S. aureus nasal colonization. METHODS: Lysostaphin was formulated into a hydrophilic cream that forms an emulsion with the secretions of the nasal mucosa, and aqueous formulations of BSYX-A110 were made containing the mucoadhesive polymers polystyrene sulfonate and chitosan. Intranasal pharmacokinetics of the drugs was measured in mice and cotton rats. RESULTS: Lysostaphin formulated in the cream increased nasal retention of the drug by 10-fold at 3 h post-cream installation and 50-fold at 24 h as compared to lysostaphin in saline drops. Furthermore, the levels of lysostaphin in the nose 24 h post-cream instillation are still above the minimum bactericidal concentration for most bacterial strains. The liquid polymer formulations also resulted in prolonged retention of antibody in the nose, with 4-fold higher levels at 3 h post-instillation as compared to antibody in saline drops. CONCLUSIONS: These results demonstrate that cream and polymer delivery systems significantly decrease the clearance rate of lysostaphin and BSYX-A110 from the nose, thereby enhancing their therapeutic potential for eradicating S. aureus nasal colonization.     

清溃口腔缓释膜的研制与临床

目的　提高药膜治疗口腔溃疡的疗效。方法　将清溃复方中药制成口腔粘膜粘附缓释药膜 ,增加膜剂的粘附力 ,延缓膜材的溶解 (崩解 )时间 ,延长药膜中药物的释放速率。结果　制成的缓释药膜的粘附力增加 ,为 4 6 4± 2 8g,T50 =171.6± 13.0 m in。结论　口腔粘膜粘附缓释药膜比普通药膜使用方便 ,疗效增加     

In situ gelling and mucoadhesive polymers: why do they need each other?

Introduction: Mucosal drug delivery is an attractive route of administration, particularly in overcoming deficits of conventional dosage forms including high first-pass metabolism and poor bioavailability. Fast drainage from the target mucosa, however, represents a major limitation as it prevents sufficient drug absorption. In order to address these problems, mucoadhesive in situ gelling drug delivery systems have been investigated as they facilitate easy application in combination with a longer residence time at the administration site resulting in more desirable therapeutic effects.

Areas covered: The present review evaluates the importance of the combination of mucoadhesive and in situ gelling polymers along with mechanisms of in situ gelation and mucoadhesion. In addition, an overview about recent applications in mucosal drug delivery is provided.

Expert opinion: In situ gelling and mucoadhesive polymers proved to be essential excipients in order to prolong the mucosal residence time of drug delivery systems. Due to this prolonged residence time both local and systemic therapeutic efficacy of numerous drugs can be substantially improved. Depending on the site of administration and the incorporated drug, combinations of different polymers with in situ gelling and mucoadhesive properties are needed to keep the delivery system as long as feasible at the target site.