Calcium and phosphorus supplemented diet increases bone volume after thirty days of high speed treadmill exercise in adult mice.

Weight-bearing exercise increases bone mass and strength. Increasing bone loading frequency during exercise can strengthen bone. Combining exercise with a calcium- and phosphorus-supplemented diet increases cortical area more than exercise alone in mice. Thus, we hypothesized that combining high-speed treadmill exercise while feeding mice a mineral-supplemented diet would lead to greater cortical area than high-speed exercise on a standard diet and low-speed exercise on a supplemented diet. Fifteen-week old male C57BL/6 mice were assigned to seven groups-(1) baseline, (2) non-exercise fed a control diet, (3) non-exercise fed a supplemented diet, (4) low-speed exercise fed a control diet, (5) low-speed exercise fed a supplemented diet, (6) high-speed exercise fed a control diet, and (7) high-speed exercise fed a supplemented diet. Mice exercised thirty days for 20 min/day at 12 m/min or 20 m/min. Tibiae were assessed by micro-CT and 4-point bending. Cortical area fraction and trabecular bone volume fraction (BV/TV) were significantly increased by the supplemented diet. High-speed exercised mice had significantly lower body weight, with no detrimental effects to bone health. Increasing running speed can decrease body weight while maintaining the benefits of exercise and nutrition on bone health. Running can lower body weight without harming bone health.

Clinical Predictors of OSA Treatment Success Following Implantation of a Hypoglossal Nerve Stimulation Device.

OBJECTIVE: To identify prognostic indicators associated with successful hypoglossal nerve stimulation (HGNS) therapy to treat obstructive sleep apnea (OSA), focusing on patients' physiologic response to awake tongue protrusion. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary care center. METHODS: We included consecutive patients with moderate-severe OSA who underwent HGNS implantation from December 2017 to December 2019. Data abstracted include standard demographics, body mass index (BMI), pre- and postoperative apnea-hypopnea index (AHI), and Friedman tongue position (FTP). Additionally, change in hypopharyngeal cross-sectional area on awake tongue protrusion was abstracted. Patients protruded their tongues, and the physician visualized change. Positive change in hypopharyngeal cross-sectional area was documented as +1 and a negative change as -1. Chi-square tests for independence and logistic regression analysis were performed to determine indicators of successful surgery. RESULTS: Thirty-nine patients were included in this study. Mean ± SD AHI decreased significantly from 43.1 ± 17.36 to 9.18 ± 8.18. Surgical success was achieved in 79.5% of patients. Variables analyzed included BMI >32, preoperative AHI, FTP, and change in hypopharyngeal cross-sectional area on awake tongue protrusion (positive, 65.8%; negative, 34.2%). Positive predictors of success were positive change in hypopharyngeal cross-sectional area (P = .0133), severe OSA (P = .0290), and FTP IIb (P < .0001). Negative predictors were BMI >32 (P = .041) and negative change in hypopharyngeal cross-sectional area (P = .02). CONCLUSION: Positive change in hypopharyngeal cross-sectional area on awake tongue protrusion and severe baseline AHI were positive predictors of successful HGNS therapy. Negative change in hypopharyngeal cross-sectional area on awake tongue protrusion and BMI >32 were negative predictors.

Light Limitation Impacts Growth but Not Constitutive or Jasmonate Induced Defenses Relevant to Emerald Ash Borer (Agrilus planipennis) in White Fringetree (Chionanthus virginicus) or Black Ash (Fraxinus nigra).

White fringetree is a host for the invasive emerald ash borer (EAB) but is of lower quality than the related and highly susceptible black ash. Field observations suggest that host trees grown in full sun are more resistant to EAB than those in shade, however the impact of light limitation on chemical defenses has not been assessed. We quantified constitutive and jasmonate-induced phloem defenses and growth patterns of white fringetree and black ash under differential light conditions and related them to EAB larval performance. White fringetree had significantly lower constitutive and induced activities of peroxidase, polyphenol oxidase, ß-glucosidase, chitinase and lignin content, but significantly higher gallic acid equivalent soluble phenolic, soluble sugar, and oleuropein concentrations compared to black ash. Multivariate analyses based on tissue chemical attributes displayed clear separation of species and induced defense responses. Further, EAB performed significantly worse on white fringetree than black ash, consistent with previous studies. Light limitation did not impact measured defenses or EAB larval performance, but it did decrease current year growth and increase photosynthetic efficiency. Overall our results suggest that phenolic profiles, metabolite abundance, and growth traits are important in mediating white fringetree resistance to EAB, and that short-term light limitation does not influence phloem chemistry or larval success.

Phages in a thermoreversible sustained-release formulation targeting E. faecalis in vitro and in vivo.

INTRODUCTION: Enterococcus faecalis is a key pathogen recovered from root canals when conventional treatment fails. Phage therapy has generated new interest in combating pathogens. A sustained-release formulation using specific phages against E. faecalis may offer an alternative approach. OBJECTIVES: To evaluate the efficacy of anti-E. faecalis phages formulated in a thermo- sustained-release system against E. faecalis in vitro and in vivo. METHODS: EFDG1 and EFLK1 phages were formulated with poloxamer P407. Gelation time, phage survival, activity and toxicity were evaluated. Lytic activity was evaluated in vitro against E. faecalis at various growth phases, including anti-biofilm activity. Methods included viable bacterial count (CFU/mL), biofilm biomass determination and electron microscopy (live/dead staining). Further evaluation included infected incisors in an in vivo rat model. Anti-E. faecalis phage-cocktail suspension and sustained-release phage formulation were evaluated by viable bacterial count (CFU/mL), histology, scanning electron microscopy (SEM) and 16S genome sequencing of the microbiota of the root canal. RESULTS: Gelation time for clinical use was established. Low toxicity and a high phage survival rate were recorded. Sustained-release phages reduced E. faecalis in logarithmic (4 logs), stationary (3 logs) and biofilm (4 logs) growth phases. Prolonged anti-biofilm activity of 88% and 95% reduction in biomass and viable counts, respectively, was recorded. Reduction of intracanal viable bacterial counts was observed (99% of enterococci) also seen in SEM. Phage treatment increased Proteobacteria and decreased Firmicutes. Histology showed reduced periapical inflammation and improved healing following phage treatment. CONCLUSION: Poloxamer P407 formulated with phages has an effective and long-lasting effect in vitro and in vivo targeting E. faecalis.

Combined mineral-supplemented diet and exercise increases bone mass and strength after eight weeks and maintains increases after eight weeks detraining in adult mice.

Exercise has long-lasting benefits to bone mass and structural strength even after cessation. Combining exercise with a calcium- and phosphorus-supplemented diet increases cortical bone mineral content (BMC), area, and yield force more than exercise alone in adult mice. These increases could also be maintained after stopping exercise if the modified diet is maintained. It was hypothesized that combining exercise with a mineral-supplemented diet would lead to greater cortical BMC, area, and yield force immediately after a lengthy exercise program and after an equally long period of non-exercise (detraining) in adult mice. Male, 16-week old C57Bl/6 mice were assigned to 9 weight-matched groups-a baseline group, exercise and non-exercise groups fed a control or mineral-supplemented diet for 8 weeks, exercise + detraining and non-exercise groups fed a control or mineral-supplemented diet for 16 weeks. Exercise + detraining consisted of 8 weeks of exercise followed by 8 weeks without exercise. The daily exercise program consisted of running on a treadmill at 12 m/min, 30 min/day. After 8 weeks, mice fed the supplemented diet had greater tibial cortical BMC and area, trabecular bone volume/tissue volume (BV/TV), bone mineral density (vBMD), yield force, and ultimate force than mice fed the control diet. Exercise increased cortical BMC and area only when coupled with the supplemented diet. After 16 weeks, both exercised and non-exercised mice fed the supplemented diet maintained greater tibial cortical BMC and area, trabecular BV/TV, vBMD, yield force, and ultimate force than mice fed the control diet. Combining exercise with a mineral-supplemented diet leads to greater bone mass and structural strength than exercise alone. These benefits remain after an equally long period of detraining. Long-term use of dietary mineral supplements may help increase and maintain bone mass with aging in adult mice.

Alternative Therapy for Patients With Obstructive Sleep Apnea/Hypopnea Syndrome: A 1-year, Single-blind, Randomized Trial of Tui Na.

Context • Obstructive sleep apnea/hypopnea syndrome (OSAHS) is among the most prevalent of sleep-related breathing disorders. No long-term follow-up studies have documented the continued success of lifestyle changes in treatment; oral appliances have an approximate 50% success rate; compliance with continuous positive airway pressure is poor, ranging from 50% to 89%; and the success rate of upper-airway surgery is only 66.4%. Therefore, some OSAHS patients seek alternative treatments. Objectives • The study intended to examine the efficacy of traditional Chinese therapeutic massage (tui na) for patients with OSAHS. Design • The research team designed a prospective study. Setting • The study took place at the outpatient clinic of the sleep center at the Kaohsiung Chang Gung Memorial Hospital (Kaohsiung, Taiwan), an academic tertiary medical center. Participants • Participants were 31 patients with moderate to severe OSAHS. Intervention • Each participant received a tui na treatment at multiple acupoints 2 ×/wk for 10 wk for approximately 15 min/session. Outcome Measures • At baseline and 3 mo after treatment, participants completed subjective measures, including (1) quality of life using a 36-item, short-form health survey (SF-36); (2) subjective snoring intensity indicated by bed-partners using a 0-10 visual analog scale (VAS); and (3) excessive daytime sleepiness (EDS) status, using a Chinese version of the Epworth Sleepiness Scale (CESS). The research team completed objective measures, including (1) polysomnography, (2) body mass index, and (3) neck circumference. Results • Twenty patients completed the full course of treatment. The apnea/hypopnea index per hour decreased from 43.8 ± 26.9 to 37.8 ± 31.7 after the treatments, with P = .049 (paired t test). The arousal index and rapid eye movement stage of sleep improved significantly. Statistically significant improvements were observed for the SF-36 on the score for the physical component summary, for its subscale for general health, for the mental component summary, and for 2 of its subscales: vitality and mental health. The VAS and the CESS showed that snoring intensity and EDS decreased significantly, respectively. No major complications occurred. Conclusions • Tui na is a feasible and safe treatment for patients with OSAHS. It can improve the quality of life, sleep architecture, snoring intensity, and EDS in patients with moderate-to-severe OSAHS. In the future, a controlled study should be considered to further investigate the effects of tui na for OSAHS.

Calcium- and Phosphorus-Supplemented Diet Increases Bone Mass after Short-Term Exercise and Increases Bone Mass and Structural Strength after Long-Term Exercise in Adult Mice.

Exercise has long-lasting benefits to bone health that may help prevent fractures by increasing bone mass, bone strength, and tissue quality. Long-term exercise of 6-12 weeks in rodents increases bone mass and bone strength. However, in growing mice, a short-term exercise program of 3 weeks can limit increases in bone mass and structural strength, compared to non-exercised controls. Short-term exercise can, however, increase tissue strength, suggesting that exercise may create competition for minerals that favors initially improving tissue-level properties over structural-level properties. It was therefore hypothesized that adding calcium and phosphorus supplements to the diet may prevent decreases in bone mass and structural strength during a short-term exercise program, while leading to greater bone mass and structural strength than exercise alone after a long-term exercise program. A short-term exercise experiment was done for 3 weeks, and a long-term exercise experiment was done for 8 weeks. For each experiment, male 16-week old C57BL/6 mice were assigned to 4 weight-matched groups-exercise and non-exercise groups fed a control or mineral-supplemented diet. Exercise consisted of treadmill running at 12 m/min, 30 min/day for 7 days/week. After 3 weeks, exercised mice fed the supplemented diet had significantly increased tibial tissue mineral content (TMC) and cross-sectional area over exercised mice fed the control diet. After 8 weeks, tibial TMC, cross-sectional area, yield force, and ultimate force were greater from the combined treatments than from either exercise or supplemented diet alone. Serum markers of bone formation (PINP) and resorption (CTX) were both decreased by exercise on day 2. In exercised mice, day 2 PINP was significantly positively correlated with day 2 serum Ca, a correlation that was weaker and negative in non-exercised mice. Increasing dietary mineral consumption during an exercise program increases bone mass after 3 weeks and increases structural strength after 8 weeks, making bones best able to resist fracture.

Targeted hypoglossal nerve stimulation for the treatment of obstructive sleep apnea: Six-month results.

OBJECTIVES/HYPOTHESIS: This feasibility study was designed to show the preliminary safety and efficacy of targeted hypoglossal neurostimulation (THN), and to identify baseline predictors of successful therapy. STUDY DESIGN: Open-label, prospective, multicenter, single-arm cohort study, conducted at seven centers in the U.S.A. and Europe. METHODS: Forty-six participants with moderate to severe obstructive sleep apnea (OSA), failing or intolerant of continuous positive airway pressure, were implanted. Primary (Apnea-Hypopnea Index [AHI], Oxygen Desaturation Index [ODI]) and secondary (Arousal Index, Epworth Sleepiness Scale Index, Sleep Apnea Quality of Life Index) outcomes were measured at baseline and compared at 6 months. Data were analyzed to identify participant characteristics that would predict success with therapy. RESULTS: Sixty-seven adverse events (AEs) were observed among 36 participants; most of the AEs were related to the implant procedure and resolved without sequelae; one device replacement was necessary. Forty-three participants showed significant (P < .01) decreases in both AHI and ODI at 6 months; 35% (15 of 43) met criteria for AHI responders and 40% (17 of 43) for ODI responders. Significant improvement was observed in all the secondary endpoints. Predictors-of-success selection criteria were identified as baseline AHI < 65/hr, baseline apnea index ≤ 30, baseline body mass index < 35, and <15 events/hr of SpO2 decrease > 10%. Seven participants met these criteria; 86% (6 of 7) were AHI responders and 86% (6 of 7) were ODI responders, indicating that THN therapy can be efficacious in a carefully selected population of OSA patients. CONCLUSIONS: This feasibility study suggests that THN therapy is likely to be safe and effective in selected patients. LEVEL OF EVIDENCE: 2b Laryngoscope, 126:2618-2623, 2016.

Comparison of the efficacy of a novel sustained release clotrimazole varnish and clotrimazole troches for the treatment of oral candidiasis.

OBJECTIVES: Candida albicans is a common fungal infection and is commensal in 40-65 % of healthy adults. The development and pharmacokinetics of a novel sustained release clotrimazole varnish (Clot-SRV) for topical oral use have been reported. The aim of this study was to compare the efficacy of this varnish with clotrimazole troche treatment of oral candidiasis. MATERIALS AND METHODS: Of the 12 patients with denture stomatitis treated for 14 days, six used Clot-SRV (study group) and six clotrimazole troches (control). The patients were instructed to use Clot-SRV (50 mg of clotrimazole) once a day, and the control group was instructed to use five troches of 10 mg clotrimazole/day. Microbiological samples were obtained from saliva, buccal mucosa, palate, and denture. The degree of erythema was recorded at three time points, and subjective opinions noted using a questionnaire. RESULTS: At the end of the study, the control group had relatively more cases of erythema on all examined surfaces; patients who applied the Clot-SRV had significantly lower levels of candida on the denture surfaces and in saliva, and had better compliance to the medication. CONCLUSIONS: The novel clotrimazole sustained release varnish may be an important part of a new protocol for oral candidiasis, with improved clinical outcomes.

Discovery of selective and orally bioavailable protein kinase Cθ (PKCθ) inhibitors from a fragment hit.

Protein kinase Cθ (PKCθ) regulates a key step in the activation of T cells. On the basis of its mechanism of action, inhibition of this kinase is hypothesized to serve as an effective therapy for autoimmune diseases such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis. Herein, the discovery of a small molecule PKCθ inhibitor is described, starting from a fragment hit 1 and advancing to compound 41 through the use of structure-based drug design. Compound 41 demonstrates excellent in vitro activity, good oral pharmacokinetics, and efficacy in both an acute in vivo mechanistic model and a chronic in vivo disease model but suffers from tolerability issues upon chronic dosing.

Therapeutic potential of thiazolidinedione-8 as an antibiofilm agent against Candida albicans.

Candida albicans is known as a commensal microorganism but it is also the most common fungal pathogen in humans, causing both mucosal and systemic infections. Biofilm-associated C. albicans infections present clinically important features due to their high levels of resistance to traditional antifungal agents. Quorum sensing is closely associated with biofilm formation and increasing fungal pathogenicity. We investigated the ability of the novel bacterial quorum sensing quencher thiazolidinedione-8 (S-8) to inhibit the formation of, and eradication of mature C. albicans biofilms. In addition, the capability of S-8 to alter fungal adhesion to mammalian cells was checked. S-8 exhibited specific antibiofilm and antiadhesion activities against C. albicans, at four- to eightfold lower concentrations than the minimum inhibitory concentration (MIC). Using fluorescence microscopy, we observed that S-8 dose-dependently reduces C. albicans-GFP binding to RAW macrophages. S-8 at sub-MICs also interfered with fungal morphogenesis by inhibiting the yeast-to-hyphal form transition. In addition, the tested agent strongly affected fungal cell wall characteristics by modulating its hydrophobicity. We evaluated the molecular mode of S-8 antibiofilm and antiadhesion activities using real-time RT-PCR. The expression levels of genes associated with biofilm formation, adhesion and filamentation, HWP1, ALS3 and EAP1, respectively, were dose-dependently downregulated by S-8. Transcript levels of UME6, responsible for long-term hyphal maintenance, were also significantly decreased by the tested agent. Both signaling pathways of hyphal formation-cAMP-PKA and MAPK-were interrupted by S-8. Their upstream general regulator RAS1 was markedly suppressed by S-8. In addition, the expression levels of MAPK cascade components CST20, HST7 and CPH1 were downregulated by S-8. Finally, transcriptional repressors of filament formation, TUP1 and NRG1, were dramatically upregulated by our compound. Our results indicate that S-8 holds a novel antibiofilm therapeutic mean in the treatment and prevention of biofilm-associated C. albicans infections.

Transepithelial transport of a natural cholinesterase inhibitor, huperzine A, along the gastrointestinal tract: the role of ionization on absorption mechanism.

During recent years there has been increasing interest in the Lycopodium alkaloid huperzine A as a potential therapeutic agent for neurodegenerative diseases. This study aimed to characterize huperzine A's permeability across the enterocyte barrier along the gastrointestinal tract with an emphasis on the effect of ionization on the drug absorption. Intestinal permeability of huperzine A was evaluated by in vitro Caco-2 and parallel artificial membrane permeation assay models and by the ex vivo Ussing chamber model. The permeability rate was strongly dependent on the degree of ionization and increased with elevation of the donor medium pH in all studied models. The transport of the unionized fraction was similar to the permeability of the markers for passive transcellular diffusion. Addition of the paracellular permeability modulator palmitoylcarnitine in the Caco-2 model led to significant enhancement in the permeability of the ionized huperzine A fraction. No evidence of active transport of huperzine A was detected in this study. The Ussing chamber model experiments showed similar drug permeability along the entire rat intestine. In conclusion, huperzine A permeates the intestinal border mainly by passive transcellular diffusion whereas some fraction, dependent on the degree of huperzine A ionization, is absorbed by the paracellular route. Huperzine A's permeability characteristics pave the way to the development of its oral extended release dosage form. The specific population of the potential users of huperzine A and the high potency of this molecule support the rationale for such a delivery.

A novel sustained-release clotrimazole varnish for local treatment of oral candidiasis.

The use of dental varnish for therapeutic purposes has been reported for fluoride or antibacterial drugs. Our objectives were to develop a sustained-release varnish containing an antifungal drug (clotrimazole) for topical application and to evaluate the release rate of the drug in human saliva in comparison with an available commercial troche and their acceptance by healthy volunteers. Following in vitro optimization of the release rate from the varnish, we have embarked on a crossover comparative study assessing the oral sensations and pharmacokinetics of a 10-mg clotrimazole oral troche versus a 10-mg sustained-release clotrimazole varnish in 14 human volunteers over a period of 5 h. Saliva samples were assessed for clotrimazole concentration by high performance liquid chromatography analysis. The volunteers' evaluation of the varnish and troche (taste, other sensory changes, convenience, and oral suitability) were recorded. At all time points, salivary clotrimazole concentrations were higher, and the terminal half-life was significantly prolonged in the varnish group in comparison to the control group. This can be attributed to continuous release of clotrimazole from the varnish formulation. The duration of the drug over the minimal inhibitory concentration, following application of the varnish, was more than threefold longer than following administration of the troche. The developed sustained-release varnish can be applied in patients at a lower frequency than troches, thus, achieving higher patient compliance and efficacy. This novel varnish application can serve as the basis for a new treatment approach to oral candidiasis, a very common chronic opportunistic infection with improved clinical outcome.

Use of a sustained release preparation of clotrimazole to treat dermatophytosis in a siamang (Hylobates syndactylus).

In November 2004, an adult male siamang (Hylobates syndactylus) from The Tisch Family Zoological Gardens-Jerusalem Biblical Zoo (Israel) presented with skin lesions on various body parts. Lesions consisted of alopecia and dry, crusty areas of hyperkeratosis. A diagnosis of dermatophytosis due to Microsporum canis was determined by fungal culture of skin scraping taken from the edge of several lesions. Treatment with various oral and topical antifungal agents such as griseofluvin, itraconozole, and lufenuron resulted in the resolution of most lesions and a decrease in size of the single remaining lesion, which continued to be culture positive for M. canis. The animal was anesthetized and an experimental sustained-release clotrimazole varnish was painted directly on the lesion. Initially there was no change in the lesion, and 2 months later a slightly altered formula was applied under anesthesia. One month later, the lesion began to reduce in size; 3 months after the start of treatment, although 2 years after the onset of clinical signs, the lesion resolved. Minimizing the number of treatments is always an advantage when dealing with exotic animals or zoological collections.

A randomized, prospective, double-blind study on the efficacy of dead sea salt nasal irrigations.

OBJECTIVE: The objective of this randomized, prospective, double-blind study was to compare nasal irrigation using hypertonic Dead Sea salt (DSS) solution with hypertonic saline in the treatment of chronic rhinosinusitis and improvement of quality of life (QOL). METHODS: With Institutional Review Board approval, 42 adults seeking treatment for chronic rhinosinusitis in a tertiary university-affiliated medical center were studied. After history and endonasal examination, computed tomography imaging, and QOL survey (Standardized Rhinoconjunctivitis Quality of Life Questionnaire [RQLQ(S)]), patients were randomized to self-administered hypertonic saline spray and irrigation twice daily or hypertonic DSS spray and irrigation. Patients were reassessed weekly and at 1 month. RESULTS: Both groups had similar symptoms and RQLQ(S) scores before treatment and had significant improvement after treatment. However, the DSS patients had significantly better symptom relief and only the DSS group showed improved RQLQ(S) scores. CONCLUSIONS: We present a short-term study providing level I evidence on the superiority of DSS over saline nasal irrigation for treatment of chronic rhinosinusitis.

Association between quantitative sensory testing, treatment choice, and subsequent pain reduction in vulvar vestibulitis syndrome.

UNLABELLED: The chronic pain syndrome of vulvar vestibulitis is a major cause of sexual dysfunction, and complete cure is not always achieved. The aim of the study was to determine whether the psychophysical characteristics of systemic pain perception predict treatment choice and outcome. Ninety women with vulvar vestibulitis syndrome were evaluated by using quantitative sensory testing with heat pain threshold measurements and pain scores for suprathreshold stimuli applied to the forearm, blood pressure measurements, and an assessment of the number of other pain disorders. Women were free to choose a surgical procedure (ie, vestibulectomy), one of the possible nonsurgical treatments (eg, biofeedback, cognitive-behavioral therapy, or hypoallergic agents), or to avoid treatment entirely. Eight months later, women reported the success of the treatment on the basis of reduction in the level of vulvar pain. Vestibulectomy demonstrated the best therapeutic effectiveness (chi2, 26.4; P <.0001). Women who chose this type of treatment had lower pain scores (P =.038) and fewer pain syndromes other than the vulvar pain (P =.025). Logistic regression analysis, controlling for the effect of vestibulectomy, indicated that lower experimental pain scores (P =.044), fewer pain disorders (P =.023), and higher systolic blood pressure (P =.039) are predictive variables for reduction of vulvar pain. An assessment of systemic pain perception might be helpful in choosing the optimal treatment and in predicting its success. PERSPECTIVE: The present study suggests that pain perception variables might be of value in the prediction of treatment choice and outcome among women with vulvar vestibulitis.

Novel gastroretentive dosage forms: evaluation of gastroretentivity and its effect on riboflavin absorption in dogs.

PURPOSE: [corrected] The purpose of this study was to design novel gastroretentive dosage forms (GRDFs) based on unfolding multilayer polymeric films, to investigate the mechanism of their gastroretentivity in dogs, and to assess the effect of compounding a narrow absorption window drug in a GRDF on the drug's absorption properties. METHODS: Dosage forms (DFs) with different dimensions and mechanical properties were administered to beagle dogs with acidic buffer (pH = 1.5), whose gastric retention time (GRT) was then determined by X-ray pictures. Concurrent administration of radiopaque markers was used to assess the effect of the GRDF and/or acidic buffer on GRT. The absorption of riboflavin from a prototype GRDF was compared with a nongastroretentive controlled-release DF and to an oral solution of the drug. RESULTS: Large DFs (> or = 2.5 x 2.5 cm) containing rigid frame had prolonged GRT (>4 h). Administration of 400 mL of acidic buffer (or water) prolonged GRT whereas the GRDF did not cause additional prolongation. The extended absorption phase (>48 h) of riboflavin administered in a GRDF led to 4-fold increased bioavailability. CONCLUSION: The combination of large dimensions with rigidity produce gastroretentivity that can be used to improve absorption properties of a model of narrow absorption window drugs in the gastrointestinal tract.