Film-coated Tablet Formulation Research Articles

Study of the Gastrointestinal Tolerance of a New Tablet Formulation of the Lopinavir/Ritonavir Antiretroviral in HIV-Infected Patients

Preliminary studies suggest that the new film-coated tablet formulation of lopinavir/ritonavir (LPV/r-fct) could cut down the rate of adverse gastrointestinal symptoms of the conventional lopinavir/ritonavir soft gelatine capsules (LPV/r-sgc). To ascertain the difference in the rate of adverse gastrointestinal symptoms in patients who switch from LPV/r-sgc to LPV/r-fct. An uncontrolled, open, prospective study including a pre/post comparison using the Gastrointestinal Symptom Rating Scale (GSRS) modified to the characteristics of the protease inhibitors. Seventy patients were included, with a mean time of treatment, with the new formulation of 77 days [confidence interval (CI) 95%: 70 to 84]. The total GSRS score was 26.96 (CI 95%: 25.02 to 28.89) in the prechange survey and 26.27 (CI 95%: 24.08 to 28.47) in the postchange survey, with a mean difference of 0.69 points (CI 95%: -1.18 to 2.55, P = 0.47). None of the questions obtained the objective of a difference of at least 2 points, previously set as a clinically significant difference. Only 1 patient dropped the study due to gastrointestinal toxicity. Our study has unearthed no clinically significant differences in the gastrointestinal tolerance profile of (LPV/r-sgc) and (LPV/r-fct), measuring this tolerance level by application of the GSRS scale.

The Rainbow Cohort: saquinavir/r is effective and well tolerated in antiretroviral therapy (ART)-naïve patients – 48-week results from Germany

Poster presentation: Purpose of the study The aim of the Rainbow Cohort is to assess the tolerability and efficacy of initiating treatment with, or switching treatment to saquinavir (SQV) 500 mg film-coated tablet formulation. We present the final 48-week subgroup analysis of antiretroviral therapy (ART)-naive patients. ...

Modafinil Trial in Attention Deficit Hyperactivity Disorder

A film-coated tablet formulation of modafinil (ProvigilR) was used to treat a total of 246 patients, ages 6 to 17 years, with attention deficit hyperactivity disorder (ADHD) at the Massachusetts General Hospital, Boston, MA, and other centers.

Efficacy and Safety of Modafinil Film–Coated Tablets in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder: Results of a Randomized, Double-Blind, Placebo-Controlled, Flexible-Dose Study

Modafinil, which is structurally and pharmacologically different from other agents that are used for the treatment of children with attention-deficit/hyperactivity disorder (ADHD), selectively activates the cortex and has low potential for abuse. Initial studies of the use of modafinil to treat ADHD showed significant improvements in the core symptoms of the disorder, namely inattention, hyperactivity, and impulsivity. This study evaluated a new formulation of modafinil (modafinil film-coated tablets) in children and adolescents with ADHD. This 9-week, multicenter, randomized, double-blind, placebo-controlled, flexible-dose study evaluated the film-coated tablet formulation of modafinil, which was titrated to an optimal dose on the basis of efficacy and tolerability (range: 170-425 mg once daily). Efficacy was assessed by clinicians who completed the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) based on interviews with teachers (School Version) and parents (Home Version) and the Clinical Global Impression of Improvement scale. Safety evaluation was based on assessments of adverse event reports, laboratory tests, vital signs, and body weight. A total of 248 subjects were randomly assigned in a 2:1 ratio, and 246 were treated with modafinil (n = 164) or placebo (n = 82). Treatment groups were comparable with respect to demographics and baseline characteristics. Intention-to-treat analysis (ITT) showed that compared with placebo, treatment with modafinil significantly improved the core symptoms of ADHD as shown by greater reductions in the ADHD-RS-IV School Version total scores from baseline to final visit (mean change [SD]: -15.0 [11.8] vs -7.3 [9.7]) (effect size: 0.69; 95% confidence interval: 0.57-0.82). Significant improvements were observed with modafinil treatment on the ADHD-RS-IV School Version at week 1, with improvements maintained throughout the study. Similar differences in symptom improvements were observed on the ADHD-RS-IV Home Version between modafinil-treated and placebo-treated patients. Treatment with modafinil also significantly reduced subscale scores for inattention and hyperactivity-impulsivity on both School and Home Versions compared with placebo. At the final visit, 48% of modafinil-treated patients were rated as "much" or "very much" improved in overall clinical condition compared with 17% of placebo-treated patients (Clinical Global Impression of Improvement). Most adverse events were mild to moderate in severity, and the majority resolved during treatment. The most commonly reported adverse events in the modafinil group were insomnia (29%), headache (20%), and decreased appetite (16%). Three percent of modafinil-treated patients and 4% of placebo-treated patients discontinued treatment because of adverse events. Modafinil film-coated tablets significantly improved ADHD symptoms at school and home as evaluated by clinicians, teachers, and parents. Treatment with once-daily modafinil was generally well tolerated, with few discontinuations as a result of adverse events.

Gamma scintigraphic evaluation of film-coated tablets intended for colonic or biphasic release

The gastrointestinal transit and in vivo drug release behaviour of a film-coated tablet formulation was investigated in five healthy human subjects using the technique of gamma scintigraphy. The film coating system consisted of a mixture of pectin, chitosan and HPMC in a ratio of 6:1:0.37 applied to 750 mg cores at a coat weight gain of 9%. The estimated mean values of the gastric emptying time (62±17 min), small intestinal transit time (219±53 min), ileocaecal junction lag time (79±30 min) and the colon arrival time (345±33 min), were similar to published values for the transit of similar sized tablets in humans. The amount of radioactive tracer released from the labelled tablets was minimal when the tablets were in the stomach and the small intestine. There was increased release of radioactivity when the tablets were in the colon due to increased degradation of the film coatings by pectinolytic enzymes resident in the colon. The pectin/chitosan/HPMC film coating system thus acts as a colonic delivery system.

Variation of Composition of an Enteric Formulation Based on Kollicoat MAE 30 D

Using a formulation described previously with Kollicoat MAE 30 D as the film-forming agent, the effect of variations in plasticizer type and quantity and talc concentration on the preparation and processing of spray-coating suspensions and the properties of isolated films and film-coated caffeine tablets prepared using them was investigated. In the preparation and processing of spray-coating suspensions, the plasticizers polyethylene glycol (PEG) 400, PEG1500, and TEC (triethyl citrate) tended to coagulate at all concentrations investigated, while Cremophor RH 40 coagulated above 10% (expressed as a percentage of the mass of the film-forming agent used). Analogous preparations using propylene glycol (PG), PEG6000, and Lutrol F 68, on the other hand, were found to be stable at all concentrations. The instability was not caused by the Kollicoat MAE 30 D polymer dispersion as such, but by interactions between the finely dispersed pigments and other formulation ingredients. Equivalent nonpigmented preparations are stable and do not coagulate. With all the plasticizers investigated, the minimum film-forming temperature (MFT) fell, albeit to differing degrees, as the amount of plasticizer increased. Similarly, the tensile strength of isolated films declined as plasticizer concentration increased, while the reverse was true as regards their elongation at break. Whereas neither the subsequent disintegration time nor the rate of release of active ingredient at pH 6.8 was significantly affected by the various plasticizer additives, the different film-coated tablet formulations with a core containing a powerful disintegrant exhibited varying degrees of permeability to simulated gastric fluid. With PEG6000, permeability increased as the plasticizer concentration increased, while Lutrol F 68 provided an optimum barrier at 20%, and PG provided a good barrier between 10% and 30%. No gastroresistance was obtained with TEC at 10%. Only the best plasticizer formulations were used in the trials with different talc concentrations, namely, those formulations with 20% PEG6000, 20% Lutrol F 68, 20% PG, and 10% PG. When talc was added, the MFT rose, reaching its maximum at 13% talc (as a proportion of the film-forming agent). In the test for gastroresistance, film-coated caffeine tablets without talc absorbed distinctly more acid than those containing talc. Above 27% talc, the acid resistance improved only insignificantly. On the other hand, during this test, only a maximum of 3% of the active ingredient was released into the gastric juice. Of the variants investigated, the formulation with 20% PG and 27% talc performed best.

Esophageal transit of risedronate cellulose-coated tablet and gelatin capsule formulations

Risedronate sodium is an orally active antiresorptive agent and a member of the pyridinyl class of bisphosphonates. It has been approved for the treatment of Paget’s disease of the bone and is under development as a chronic therapy for the treatment and prevention of osteoporosis. A novel cellulose film-coated tablet formulation was developed to optimize esophageal transit of this bisphosphonate. The aim of the present study was to compare the esophageal transit of the film-coated tablet formulation of risedronate with its original gelatin capsule dose form. A total of 25 elderly, healthy volunteers (mean 66 years), who were dysphagia-free, participated in this randomized cross-over study. On separate occasions, volunteers swallowed radiolabeled placebo formulations with 50 ml water. Dynamic images with participants in a sitting position were recorded for 10 min using a gamma camera. Scintigraphic imaging showed a delay in esophageal transit (greater than 15 s) in 28% of patients in the capsule group but in none of the tablet group ( P<0.05). The mean transit times of the capsules and tablets were 23.8 and 3.3 s, respectively. Esophageal transit of film-coated tablets was faster than gelatin capsules, suggesting that film-coated tablets would be the appropriate formulation for all pivotal trials with risedronate and for subsequent commercialization.

Comparative Bioavailability of Two Oral Nimodipine Formulations after Administration to 24 Healthy Volunteers

Objective and Study Participants: To investigate the comparative bioavailability of two oral 30mg film-coated tablet formulations of nimodipine, Brainal® (test formulation) and Nimotop® (reference formulation) after replicate administration of a single 60mg dose (2 × 30mg) of both formulations to 24 healthy volunteers.

Effect of formulation factors and food intake on the bioavailability of erythromycin stearate tablets

The bioavailability of 3 commercial erythromycin tablet formulations: film-coated stearate, enteric-coated stearate and enteric-coated erythromycin base, was compared in a single-dose cross-over study on 15 healthy volunteers. The tablets were administered to fasted subjects and in a mode where drug administration was followed by a standardized breakfast. The bioavailability of the film-coated tablet was enhanced by food intake, whereas food impaired the bioavailability of the other two formulations. From the bioavailability study results and from the tablets' in vitro disintegration properties it was concluded that it is not necessary to protect erythromycin stearate by an enteric-coating, but with a film-coating withstanding low pH and susceptible of disintegrating rapidly at pH values above 4.5. On the basis of these results a new film-coated erythromycin stearate tablet formulation was developed which had the desired in vitro disintegration properties and showed good bioavailability when administered just prior to a standardized breakfast. It is suggested that the proposed in vitro test can be useful in controlling the production of the novel tablet formulation.

Comparative Evaluations of Aqueous Film Coated Tablet Formulations by High Humidity Aging

Compressed tablets of ticlopidine hydrochloride were coated with three aqueous film coating formulations and aged under 95% relative humidity at 23° and 37°. The in vitro dissolution of the drug from tablets coated with the formulation containing polymethacrylic acid esters before aging was slower than the tablets coated with the formulations containing hydroxypropyl methylcellulose or ethylcellulose dispersion. On aging, the in vitro drug dissolution of the coated and uncoated tablets decreased and the decrease depended on the film forming excipient in the coating formulation and the temperature of aging. The tablets coated with the formulation containing polymethacrylic acid esters dissolved very slowly after aging. Higher moisture contents of the tablets after aging under 95% relative humidity at 23° compared to 37° resulted in a consistently lower tablet crushing strength. The tablets coated with the formulation containing 10% hydroxypropy1 methylcellulose showed a smaller decrease in the tablet crush...