Fast Dissolving Oral Films Research Articles

Formulation and Evaluation of Fast Dissolving Oral Films of Diazepam

Oral films dissolve rapidly along with drug in mouth and majority of the drug is absorbed through buccal/oral mucosa in to systemic circulation avoiding first pass metabolism. The aim of present investigation was to formulate the Fast dissolving oral films (FDOF) of Diazepam an anti epileptic drug which is normally administered by intramuscular route or as rectal suppository in acute conditions of seizure emergencies. Oral films were prepared by solvent casting method using HPMC E3, E5, and E15 as a film formers and propylene glycol, PEG 400 as plasticizers and evaluated for mechanical properties, disintegration and in vitro dissolution. All formulations showed good mechanical properties and in vitro drug release. The optimized (F4A) Formulation (HPMC E5 and PEG 400) Exhibited drug release of 99.89% in 15 minutes which was significantly high when compared to marketed tablet valium (68.81%).

FORMULATION AND EVALUATION OF FAST DISSOLVING ORAL FILMS OF PROCHLORPERAZINE MALEATE

The objective of the present study was to prepare and evaluate fast-dissolving oral films of prochlorperazine maleate (PCM), in order to enhance the bioavailability of the drug and to provide rapid onset of action thereby improving patient compliance. The solubility of the drug was increased by preparing inclusion complex with 2-hydroxypropyl-β-cyclodextrin (2HPβCD) and then incorporating it into the fast dissolving films. The fast-dissolving films of PCM were prepared by solvent casting method using different film forming polymers such as HPMC E15 and HPMC E5, either as single polymer or combination of the two. The film formulations were evaluated for various physico-chemical parameters. All formulations released more than 85% of the drug within 15 minutes. Formulation F4 showed best in vitro drug release profile. From the ex vivo study it was found that 94.79% of drug permeated through the porcine oral mucosa from the optimized formulation F4 within 60 mins.

Formulation and evaluation of rapid dissolving films of pravastatin sodium

The concept of Fast dissolving drug delivery system offers a solution for those patients having difficulty in swallowing tablets/capsules etc. This work investigated the possibility of developing Pravastatin sodium rapid dissolving films allowing fast, reproducible drug dissolution in the oral cavity, decreases the hyperlipidemia effect in patients in less time and enhances the patient compliance The fast-dissolving oral films of Pravastatin Sodium prepared using different film-forming materials HPMC E5 and Polyvinyl alcohol by the solvent-casting method which is simple and cost effective. The prepared films were subjected to different evaluation parameters like morphological properties, film thickness, folding Endurance, Surface pH, content uniformity, in vitro disintegration time and in vitro dissolution studies. The optimized formulation was subjected to stability studies, revealed that no significant changes occur after 1 month of test period. Results of FTIR data of optimized formulation (F10) revealed that there was no incompatibility observed between the drug and excipients used in the formulation. These findings suggest that the fast dissolving oral film containing Pravastatin sodium is considered to be potentially useful for the treatment of hyperlipedemia where quick onset of action is desirable.

Oral delivery of ivermectin using a fast dissolving oral film: Implications for repurposing ivermectin as a pharmacotherapy for alcohol use disorder

Individuals suffering from an alcohol-use disorder (AUD) constitute a major health concern. Preclinical studies in our laboratory show that acute and chronic intraperitoneal (i.p.) administration of ivermectin (IVM) reduces alcohol intake and preference in mice. To enable clinical investigation to use IVM for the treatment of an AUD, development of an oral formulation that can be used in animals as well as long-term preclinical toxicology studies are required. The present work explores the use of a promising alternative dosage form of IVM, fast-dissolving oral films (Cure Pharmaceutical®), to test the efficacy and safety of oral IVM in conjunction with alcohol exposure. We tested the effect of IVM (0.21 mg) using a fast-dissolving oral film delivery method on reducing 10% v/v alcohol (10E) intake in female C57BL/6 mice using a 24-h access two-bottle choice paradigm for 6 weeks (5 days per week). Differences in ethanol intake, preference for ethanol, water intake, fluid intake, food intake, changes in mouse and organ weights, as well as histological changes to kidney, liver, and brain were analyzed. The IVM group drank significantly less ethanol over the 30-day period compared to the placebo (blank strip) and the no-treatment groups. Organ weights did not differ between the groups. Histological evaluation showed no differences in the brain and kidney between groups. In the liver, there was a slight increase in the incidence of microvesicular fatty and degenerative changes of the animals receiving the thin strips. No overt hepatocellular necrosis or perivascular inflammation was noted. Overall, these data support the use of this novel method of oral drug delivery for longer-term studies and should facilitate FDA required preclinical testing that is necessary to repurpose IVM for treatment of an AUD.

A solid phospholipid-bile salts-mixed micelles based on the fast dissolving oral films to improve the oral bioavailability of poorly water-soluble drugs

The phospholipid-bile salts-mixed micelles (PL-BS-MMs) are potent carriers used for oral absorption of drugs that are poorly soluble in water; however, there are many limitations associated with liquid formulations. In the current study, the feasibility of preparing the fast dissolving oral films (FDOFs) containing PL-BS-MMs was examined. FDOFs incorporated with Cucurbitacin B (Cu B)-loaded PL-sodium deoxycholate (SDC)-MMs have been developed and characterized. To prepare the MMs and to serve as the micellar carrier, a weight ratio of 1:0.8 and total concentration of 54 mg/mL was selected for the PL/SDC based on the size, size distribution, zeta potential, encapsulation efficiency, and morphology. The concentration of Cu B was determined to be 5 mg/mL. Results showed that a narrow size distributed nanomicelles with a mean particle size of 86.21 ± 6.11 nm and a zeta potential of −31.21 ± 1.17 mV was obtained in our optimized Cu B-PL/SDC-MMs formulation. FDOFs were produced by solvent casting method and the formulation with 50 mg/mL of pullulan and 40 mg/mL of PEG 400 were deemed based on the physico-mechanical properties. The FDOFs containing Cu B-PL/SDC-MMs were easily reconstituted in a transparent and clear solution giving back a colloidal system with spherical micelles in the submicron range. In the in vitro dissolution test, the FDOFs containing Cu B-PL/SDC-MMs showed an increased dissolution velocity markedly. The pharmacokinetics study showed that the FDOFs containing PL-SDC-MMs not only kept the absorption properties as same as the PL-SDC-MMs, but also significantly increased the oral bioavailability of Cu B compared to the Cu B suspension (p < 0.05). This study showed that the FDOFs containing Cu B-PL/SDC-MMs could represent a novel platform for the delivery of poorly water-soluble drugs via oral administration. Furthermore, the integration with the FDOFs could also provide a simple and cost-effective manner for the solidification of PL-SDC-MMs.

FORMULATION AND EVALUATION OF RAPIDLY DIS INTEGRATING FILM OF AMLODIPINE BES YLATE

Fast-dissolving drug-delivery systems were first developed in the late 1970s as an alternative to tablets, capsules, and syrups. Fast dissolving oral films (FDOFs) are the most advanced form of  oral solid dosage form due to more flexibility and comfort. It improve the efficacy of APIs by dissolving within minute in oral cavity after the contact with less saliva as compared to fast dissolving tablets, without chewing and no need of water for admin istration. The FDOFs place as an alternative in the market due to the consumer’s preference for a fast dissolving product over conventional tablets / capsules. The oral thin-film technology is still in the beginning stages and has bright future ahead because it fulfils all the need of patients. Eventually, film formulations having drug/s will be commercially launched using the oral film technology. In the present study fast dissolving film of  Amlodipine Besylate was prepared using sodium alginate as film forming polymer. To decrease the disintegration time of formulationssodium starch glycolate was used as disintegrating agent. A full 32factorial design was applied using concentration of polymer and disintegrant as independent variable and disintegration time and % cumulative drug release as dependent variable. Response surface curves were plotted. Batch F6 was found to be the optimized batch as its disintegration was completed within the minimum time as compared to all other batches. The formulation (F6) was also showing sufficient drug release after 6 min. All the nine formulation was showing approximately 70-85% drug release after 6 min

Comparative investigations on different polymers for the preparation of fast-dissolving oral films

The aim was to compare different film-forming materials used for the preparation of fast-dissolving oral films. Films were prepared with and without caffeine and caffeine citrate as model drugs. The disintegration/dissolution behaviour of films was investigated using the newly developed slide frame method and Petri dish method. Films were also characterised by dynamic vapour sorption. All films dissolved within 40 s. Drug-loaded films disintegrated more slowly than the equivalent drug-free formulations. Disintegration/dissolution was fastest with films made from the carboxymethyl cellulose C 30 PA 09 (drug-free < 5 s, drug-loaded < 10 s). Dissolution times for drug-loaded oral films made from C 30 PA 09 and HM 6 PA 2910 (hydroxypropyl methyl cellulose) differed significantly (alpha= 0.05). Dynamic vapour sorption studies revealed higher water absorption ratios for carboxymethyl cellulose films, and these were sticky and difficult to handle. This case study showed that hydroxypropyl methyl cellulose was the most suitable film-forming material for drug-free and caffeine-loaded films, providing fast dissolution films that were not sticky and were easy to handle.

Monitoring crystallisation of drugs from fast-dissolving oral films with isothermal calorimetry

The aim of this study was to evaluate the potential of isothermal calorimetry to monitor and characterize crystallisation in drug-loaded fast-dissolving oral films. Films of polyvinylpyrrolidone (PVP) containing indomethacin were cast into glass ampoules; stability was assessed by monitoring the power changes occurring with time. Three grades of PVP (K10, K25 and K40, where the number multiplied by 1000 gives the average molecular weight) were used. Indomethacin was seen to crystallise from all PVP grades over ca. 24–48 h at two study temperatures (25 and 37 °C), as denoted by a large exothermic event. At 25 °C the exothermic event was a single peak; at 37 °C two peaks were observed. Subsequent analysis of the crystals with differential scanning calorimetry (DSC) and polarized light microscopy determined that the stable γ-polymorph of indomethacin formed at 25 °C while both the γ- and metastable α-polymorphs formed at 37 °C. The calorimetric data were converted to relative crystallinity as a function of time and analysed with three crystallisation models (Avrami, Tobin and Urbanovici–Segal) to determine crystallisation kinetics. Of the three models applied the Urbanovici–Segal model best described the data, although this may be because this model contains a term that effectively accounts for deviation from the Avrami model. The rate constants determined were broadly consistent irrespective of the model used. Increasing polymer molecular weight did not generally affect the crystallisation rate, although an increase in temperature did result in a concomitant increase in crystallisation rate. The data suggest that isothermal calorimetry is able to monitor drug crystallisation in polymer films and therefore the technique could be a useful tool for conducting stability assays for fast-dissolving oral medicines.