Solid Dosage Research Articles

An Exploration of The Potential of Natural Super Disintegrating Agents in Pharmaceutical Formulations: A Review

This review delves into the use of natural super disintegrating agents in pharmaceutical drug formulations. Disintegrants are incorporated into these formulations to aid in breaking down tablets and capsules, promoting rapid dissolution by facilitating their dispersion into smaller particles. Super disintegrants, distinguished by their notable swelling capacity, play a pivotal role in expediting drug disintegration within the gastrointestinal tract. The selection of an appropriate super disintegrant hinges on several factors, including chemical compatibility, swelling potential, disintegration speed, particle size, cost, manufacturing methods, and adherence to regulatory standards. The piece elucidates the diverse mechanisms through which super disintegrants foster the disintegration of solid dosage forms. These mechanisms encompass swelling, wicking, heat-induced wetting, chemical reactions, particle repulsion, and deformation recovery. A comprehensive grasp of super disintegrants' properties and mechanisms is indispensable for ensuring the effectiveness, safety, and cost-efficiency of drug formulations. This review article critically examines existing literature, offering a valuable resource for researchers and pharmaceutical professionals engaged in the development of efficient and safe pharmaceutical products.

Overview in EMA and FDA Approved Novel Drugs in the Years 2020, 2021 and 2022.

Introduction: the drug approval is essential to any drugs to get in the market for use by patients. The current overview have been focuses on novel drugs approvals by European medicine agency (EMA) and food and drug administration (FDA).Objective: The researchers have been focused on the different between the EMA and FDA novel drugs approval during three years. Method: Throughout extracts the data from EMA and FDA and other sources and analyze the results like orphan drugs, dosage form, number of approvals, route of administration, pharmacotherapeutic class of novel drugs in both agencies.Result: In 2020, the EMA and FDA approved 39 and 53 new drugs, respectively. In 2021, the EMA approved 54 drugs, while the FDA approved 50 drugs for 2022 EMA approved 41 drugs, while the FDA approved 37. For orphan drug designation FDA had higher orphan designation than the EMA, in term of route of administration the vast majority of FDA approved drugs were parenteral drugs.Over the last three years. On the other hand, EMA approved parenteral drugs were also the highest percent. Likewise in terms of dosage form, the solid dosage forms in both EMA and FDA had the upper hand except for 2021 in the FDA. in the pharmacotherapeutic class of the EMA and FDA show high percent of antimicrobial agents, antineoplastic agents, and endocrine agents. Conclusion: The drug approval processes of the EMA and FDA exhibit similarities and differences. This Variations highlight the distinct regulatory considerations and priorities of each agency. Understanding these factors is vital for company, healthcare providers and general knowledge

Determination of Canagliflozin, Dapagliflozin, and Empagliflozin in Pharmaceutical Solid Dosage Forms by the HPLC Method

Determination of Canagliflozin, Dapagliflozin, and Empagliflozin in Pharmaceutical Solid Dosage Forms by the HPLC Method

Importance of Appropriate Medication Administration in Patients with Nasogastric Feeding Tube

Solid dosage forms like modified release and enteric coated formulations are considered inappropriate for nasogastric feeding tube (NGFT) administration due to varying pharmacokinetics which could lead to inadequate therapeutic responses or toxicity. An analysis was conducted to assess the appropriateness of prescribed medicines for NGFT administration in hospital inpatients so that physicians can be sensitized to the importance of this. In this cross-sectional study conducted in a large tertiary care centre, prescription data of in-patients with nasogastric feeding tube (NGFT) were retrieved through electronic pharmacy transactions. Adult patients who were admitted in the hospital for more than one day and were dispensed a NGFT were included. The appropriateness of medicines administered through NGFT was assessed using standard published literature. Details of medicines that were categorized as inappropriate were collated and analysed. In case of inappropriate prescribing, availability of appropriate dosage forms was also determined. A total of 510 patients were found eligible for analyses. Majority of the patients were dispensed at least one inappropriate dosage form. Among the dispensed oral solid dosage forms, 16.38% were found to be inappropriate for NGFT administration. Of these, 21.41% were dispensed on same day as the NGFT, 34.67% were dispensed before the NGFT and were continued throughout the hospital stay and 43.92% were dispensed within or after 24 hours of NGFT dispensation. These findings will improve awareness among healthcare professionals about the need for appropriate administration of oral formulations in patients intubated with NGFT. Keywords: Inappropriate Dosage Forms, Nasogastric Feeding Tube, Appropriate Dosage Forms, Modified Release Formulations

Characterization of Khaya Senegalensis Gum: Effects of Drying Methods on the Physicochemical Properties

The study was aimed to assess the effect of drying methods on physicochemical properties of Khaya senegalensis gum. Gum exudates obtained from the bark of Khaya senegalensis plant was extracted and subjected to freeze drying and vacuum oven drying. Gel permeation chromatography, Elemental analysis, attenuated total reflectance Fourier transforms Infra red spectroscopy were used to characterize the gum. The effect of drying methods on the gum samples were assessed based on Differential scanning calorimetry, Scanning electron microscopy, Dynamic vapour sorption, particle size analysis via laser diffraction techniques, colour and density measurements. An average molecular weight of 60 KDa expressed as the Dextran equivalent and a polydispersity of 2.17 with a retention time of 18,485 min was recorded for the vacuum dried gum. The vacuum dried gum occurred as irregular discreet coarse particles, containing both amorphous and crystalline portions due to a glass transition of 65◦ and melting temperature of 182.35◦C. It also displayed excellent flow and compressibility properties whereas the freeze-dried gum appeared flaky, porous with large surface area. The mechanism of water sorption was found to be initial surface adsorption and subsequently bulk absorption for both freeze dried and vacuum dried gum samples. The coarseness, water sorption and retention ability of the vacuum dried gum provides a potential for its use as a disintegrant in solid dosage formulations whereas the freeze-dried gum will be suitable for use as a binding agent due to its smaller particle sizes that enhanced solubility. Furthermore, the presence of nitrogen in Khaya senegalensis gum structure explains its partial solubility and the azo aromatic group suggests biodegradability and candidature for drug delivery to the colon. Keywords: Khaya senegalensis Gum; Average Molecular Weight; Amorphous; Crystalline; Direct Compression Excipient; Disintegrant 2 Freeze and vacuum dried Khaya senegalensis gum characterization

Comparison of Titanium Dioxide-containing and Titanium Dioxide-free Film Coating Systems

Titanium dioxide (TiO2) is an important white pigment and opacifier that has been used in the pharmaceutical industry for over 50 years. It has been included ubiquitously in coloured coating systems and therefore many medicines. Its use in oral solid dosage forms, however, is now under scrutiny due to data linking TiO2 particle inhalation with DNA damage. This also caused the European Union to ban its use as a food additive. Consequently, material suppliers have launched several TiO2-free (TF) pharmaceutical coatings. In this study, two TF coatings based on different pigments were compared with a traditional TiO2-containing coating assessing covering and colour quality. The TF coatings both showed a comparable quality in these parameters to the TiO2-containing coating. The differences in colour and the degree of whiteness were also quantitatively measured and compared using CIELAB measurements derived from optical lens readings. The colour analysing tool used limited this data.

Effect of lubricants on the properties of tablets compressed from varied size granules

Magnesium stearate (MgSt) is one of the most widely used solid lubricants in oral solid dosage forms. However, MgSt can negatively impact the tablets, decreasing their mechanical properties and lengthening disintegration/dissolution times. The aim of the present study was to compare the effect of MgSt and Sodium Stearyl Fumarate (SSF) lubricants on the physical characteristics of immediate release caffeine tablets compressed using granules of different sizes. Overall, the results demonstrate that using SSF as a lubricant significantly enhances tablet mechanical strength and reduces disintegration/wetting times for all granule sizes used to compress tablets. With smaller granules, SSF tends to be more effective. Over-lubrication with SSF leads to a decrease in tablet hardness as well, though to a significantly lesser extent than over-lubrication with MgSt.

A Colourful Way to Unravel the Important Fluidization-Related Granule Size Effect on Semi-Continuous Drying.

Continuous twin screw wet granulation (TSWG) systems are possible pathways for oral solid dosage manufacturing in the pharmaceutical industry. TSWG requires a drying step after granulation before the tableting process. Typically, semi-continuous fluidized bed dryers (FBDs) are used for this purpose. At the same time, the pharmaceutical sector is interested in mathematical prediction models to save resources during the early drug product development (DPD) stage or to control manufacturing. Several authors have already developed prediction models for semi-continuous drying processes. However, these model structures reported systematic prediction offsets, which could be related to the incomplete implementation of fluidization and granule segregation phenomena. This study evaluates the complex fluidization behavior of wet granules in industrially relevant semi-continuous FBDs. A transparent perspex version of the dryer was used for the analysis of bed height, pressure drop, porosity, segregation, and spatial heating patterns at varying process settings. The investigated behaviors of the fluidizing bed will be helpful to derive phenomenological (sub)models for the detailed description of segregation in the semi-continuous fluidized bed system. In this study, it was found that semi-continuous FBDs are characterized by a change in fluidization regime from plug flow to a bubbling bed at the moment that the granule bed slumps. Secondly, the presence of size-based vertical segregation phenomena as well as spatial temperature differences were proven. The experimental results suggest that larger granules are dried under more intense drying conditions than smaller granules.

Probing the Protein-Excipient Interaction in the Orally Delivered Protein by Solid-State Hydrogen-Deuterium Exchange Mass Spectrometry and Molecular Dynamics.

The oral administration of protein therapeutics in solid dosage form is gaining popularity due to its benefits, such as improved medication adherence, convenience, and ease of use for patients compared to traditional parental delivery. However, formulating oral biologics presents challenges related to pH barriers, enzymatic breakdown, and poor bioavailability. Therefore, understanding the interaction between excipients and protein therapeutics in the solid state is crucial for formulation development. In this Letter, we present a case study focused on investigating the role of excipients in protein aggregation during the production of a solid dosage form of a single variable domain on a heavy chain (VHH) protein. We employed solid-state hydrogen-deuterium exchange coupled with mass spectrometry (ssHDX-MS) at both intact protein and peptide levels to assess differences in protein-excipient interactions between two formulations. ssHDX-MS analysis revealed that one formulation effectively prevents protein aggregation during compaction by blocking β-sheets across the VHH protein, thereby preventing β-sheet-β-sheet interactions. Spatial aggregation propensity (SAP) mapping and cosolvent simulation from molecular dynamics (MD) simulation further validated the protein-excipient interaction sites identified through ssHDX-MS. Additionally, the MD simulation demonstrated that the interaction between the VHH protein and excipients involves hydrophilic interactions and/or hydrogen bonding. This novel approach holds significant potential for understanding protein-excipient interactions in the solid state and can guide the formulation and process development of orally delivered protein dosage forms, ultimately enhancing their efficacy and stability.

Unlocking the Potential: Synergistic Effects of Solid SNEDDS and Lyophilized Solid Dispersion to Enhance Stability Attributes.

Among lipid-based formulations, self-nanoemulsifying drug delivery systems (SNEDDS) have captured a spotlight, captivating both academia and the pharmaceutical industry. These remarkable formulations offer a valuable option, yet their liquid form presents certain challenges for delivering poorly soluble drugs. Ensuring compatibility with capsule shells, maintaining physical and chemical stability, and understanding their impact on lipolysis remain vital areas of exploration. Therefore, the incorporation of this liquid formulation into a solid dosage form (S-SNEDDS) is compelling and desirable. S-SNEDDSs, prepared by adsorption, enhances formulation stability but retards drug dissolution. This study aims to design drug-free solid S-SNEDDS + solid dispersion (SD) as a novel combination to enhance cinnarizine (CN) stability upon storage while maintaining enhanced drug dissolution. Drug-free liquid SNEDDSs were solidified using Neusilin® US2 at a 1:1 ratio. CN-SDs were prepared using freeze-drying technology. The SDs that were developed underwent characterization using various techniques, including scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). In vitro lipolysis studies were conducted to evaluate the effect of the combined system on the performance of the formulation upon exposure to enzymes within biorelevant media. In agreement with the DSC and XRD results, FTIR confirmed the amorphization of CN within the freeze-dried solid dispersion (FD-SD) systems. The in vitro lipolysis studies showed that the drug-free S-SNEDDS + SD combination was able to maintain a significant portion of the initial CN in solution even in the presence of lipase for up to 30 min. The accelerated stability studies showed that the drug-free S-SNEDDS + SD combination maintained 96% intact CN in an amorphous state and more than 90% release at pH 1.2 for up to 6 months, while the dissolution profile at pH 6.8 showed a significant drop in CN release upon storage. Overall, the developed formulation could be a potential technique to enhance the dissolution of weakly basic drugs that possess challenging stability limitations.

Pharmaceutical-technological Studies on the Development of Optimal Composition of Antibacterial Preparation Sekstafag® (Piobacteriophage Polyvalent) Capsules

Introduction. Nowadays liquid combined therapeutic and prophylactic bacteriophages produced by various manufacturers are widely used. In order to expand the Russian market with highly effective antibacterial phagopreparations it is urgent to develop solid dispersed dosage forms of bacteriophages in the form of solid capsules.Aim. Optimization of biomass composition for encapsulation of antibacterial drug Sekstafag® (Piobacteriophage polyvalent) capsules.Materials and methods. The object of research for the development of encapsulated antibacterial drug is liquid combined polyvalent bacteriophage Sekstafag® (Piobacteriophage polyvalent), which is a mixture of sterile filtrates of six phagolysates of bacteria Staphylococcus spp., Streptococcus spp., Proteus spp., Pseudomonas aeruginosa, Klebsiella pneumoniae, enteropathogenic Escherichia coli. Pharmaceutical-technological tests were carried out according to GF. Granulate was investigated according to the following parameters: description, bulk density, friability. Solid capsules Sekstafag® were tested by the following parameters: mass uniformity, disintegration, acid resistance of bacteriophages in capsules, dissolution. The lytic activity of bacteriophages was evaluated by Appelman’s method. Optimization of Sekstafag® drug formulation in the form of capsules was carried out using generalized Harrington’s desirability function.Results and discussion. In order to optimize the composition of biomass for encapsulation, pharmaceutical compositions consisting of combined bacteriophage Sekstafag® and auxiliary substances were prepared. The influence of excipients on the technological quality parameters of mixtures and capsules of model compositions was studied. According to the empirical system of preferences (desirability) it was revealed that the optimal pharmaceutical-technological characteristics (granulate description, bulk density, bulkiness, capsule mass uniformity, disintegrability, lytic activity, acid resistance of bacteriophage, dissolution) are possessed by the model composition containing combined polyvalent Sekstafag®, methylcellulose, sorbitol, lactose, pectin, sodium alginate, calcium carbonate, magnesium stearate. Originality of the developed composition Sekstafag® (Piobacteriophage polyvalent) in the form of capsules is confirmed by the patent of the Russian Federation № 2660355 "Antibacterial pharmaceutical composition for oral use containing bacteriophages". The drug Sekstafag® (Piobacteriophage polyvalent) capsules, is stable when stored for 18 months at temperatures from 2 to 8 °C.Conclusion. As a result of the conducted complex pharmaceutical-technological research using Harrington’s desirability function the optimal composition of antibacterial preparation Sekstafag® (Piobacteriophage polyvalent) in the form of hard capsules No. 2 was developed.

Solidifying Fenofibrate Nanocrystal Suspension: A Scalable Approach via Granulation Method

The pharmaceutical industry has highlighted particle-size reduction via preparing aqueous suspensions containing nano- or submicron drug particles. Owing to the risk of agglomeration and complications during the manufacturing of solid dosage forms, the problems associated with the solidification of nanosuspensions need to be addressed. Herein, the nanocrystallized suspension of fenofibrate (Feno) was prepared using the wet-milling technique, and then two solidification methods, mixing (liquid mixing) and granulation (dry powder blending and wet massing) methods, were investigated. The solidification process involved the adsorption of Feno as a very thin layer on the high-surface-area Florite® to prevent drug accumulation. The critical quality attributes, particle size and dissolution rate, were performed. Infrared spectroscopy, X-ray diffraction, differential scanning calorimetry, and scanning electron microscopy were also used to monitor the existence and physical state of drug molecules in the carrier. The final solidified powders and tablets containing Feno nanocrystals improved the dissolution profile (>90% in 15 min), in which the physical properties of Feno were maintained during solidification and tableting. In general, the granulation method is more advantageous than the mixing method in terms of maintaining amorphous proportion and dissolution rate. These results implied a potential approach for manufacturing solid dosage forms from nanoscale products.

Quantitative analysis of cephalexin in solid dosage form by Raman spectroscopy and chemometric tools

Objective To use Raman Spectroscopy for qualitative and quantitative evaluation of pharmaceutical formulations of active pharmaceutical ingredient (API) of Cephalexin. Significance Raman Spectroscopy is a noninvasive, nondestructive, reliable and rapid detection technique used for various pharmaceutical drugs quantification. The present study explores the potential of Raman Spectroscopy for quantitative analysis of pharmaceutical drugs. Method For qualitative and quantitative analysis of Cephalexin API, various standard samples containing less and more concentration of API than commercial tablet was prepared. To study spectral differences, the mean plot of all the samples was prepared. For qualitative analysis, Principal Component Analysis (PCA) and for quantitative analysis Partial Least Square Regression analysis (PLSR) was used. Both of these are Multivariate data analysis techniques and give reliable results as published in previous literature. Results PCA model distinguished all the Raman Spectral data related to the various Cephalexin solid dosage formulations whereas the PLSR model was used to calculate the concentration of different unknown formulations. For the PLSR model, RMSEC and RMSEP were determined to be 3.3953 and 3.8972, respectively. The prediction efficiency of this built PLSR model was found to be very good with a goodness of the model value (R2) of 0.98. The PLSR model also predicted the concentrations of Cephalexin formulations in the blind or unknown sample. Conclusion These findings demonstrate that the Raman spectroscopy coupled to PLSR analysis could be regarded as a fast and effectively reliable tool for quantitative analysis of pharmaceutical drugs.

Preformulation: Development of Solubility, UV and FTIR estimation of Phytobioactive Antifungal Compounds Allicin

When developing new dosage forms, compatibility tests between excipients and active pharmaceutical ingredients (API) are essential for preformulation. An API’s chemical composition, stability, and bioavailability, as well as its safety and therapeutic efficacy, can all be affected by possible physical and chemical interactions with its excipients. Solid dosage forms are typically less stable than the constituents of their API. Even though testing for API-excipient compatibility is important, there isn’t a universally accepted method for assessing these kinds of interactions. The oily, yellow material that gives garlic its distinct smell is called allicin. It’s a thioester of sulfenic acid. Another name for it is alyl thiosulfinate. Its interaction with proteins containing thiols and antioxidant activity are what give it its biological activity. In the present work various preformulation parameters of allicin was estimated and reported.

Quality by Design Approaches in Pharmaceutical Development and Solid Dosage Forms Production: A Narrative Overview

Quality by Design (QbD) is an essential approach to pharmaceutical development and manufacturing that has garnered significant attention in recent years. Quality in services, products, and procedures equates to customer satisfaction. Consequently, it facilitates a transition in the pharmaceutical sector and the Food and Drug Administration (FDA) toward a more scientific, risk-based, comprehensive, and proactive drug development strategy. The pharmaceutical industry is actively seeking new solutions to ensure product quality and efficiency. This paper provides a comprehensive overview of QbD principles and their application in the pharmaceutical industry. The benefits of implementing QbD principles are discussed, encompassing increased efficiency, reduced costs, and improved product quality, safety, and efficacy. As the pharmaceutical industry continues to evolve, QbD will remain a crucial aspect of drug development and manufacturing. This article aims to provide pharmaceutical professionals with a comprehensive understanding of the QbD approach.

In Vitro and In Vivo Performance of Pickering Emulsion-Based Powders of Omega-3 Polyunsaturated Fatty Acids.

Omega-3 polyunsaturated fatty acids (n-3 PUFA) are essential nutrients for human health and have been linked to a variety of health benefits, including reducing the risk of cardiovascular diseases. In this paper, a spray-dried powder formulation based on Pickering emulsions stabilized with cellulose nanocrystals (CNC) and hydroxypropyl methylcellulose (HPMC) has been developed. The formulation was compared in vitro and in vivo to reference emulsions (conventional Self-Emulsifying Drug Delivery System, SEDDS) to formulate n-3 PUFA pharmaceutical products, specifically in free fatty acid form. The results of in vivo studies performed in fasted dogs showed that Pickering emulsions reconstituted from powders are freely available (fast absorption) with a similar level of bioavailability as reference emulsions. In the studies performed with dogs in the fed state, the higher bioavailability combined with slower absorption observed for the Pickering emulsion, compared to the reference, was proposed to be the result of the protection of the n-3 PUFAs (in free fatty acid form) against oxidation in the stomach by the solid particles stabilizing the emulsion. This observation was supported by promising results from short-term studies of chemical stability of powders with n-3 PUFA loads as high as 0.8 g oil/g powder that easily regain the original emulsion drop sizes upon reconstitution. The present work has shown that Pickering emulsions may offer a promising strategy for improving the bioavailability and stability as well as providing an opportunity to produce environmentally friendly (surfactant free) and patient-acceptable solid oral dosage forms of n-3 PUFA in the free fatty acid form.

Optimizing Energy Efficiency of a Twin-Screw Granulation Process in Real-Time Using a Long Short-Term Memory (LSTM) Network.

Traditional pharmaceutical manufacturing processes for solid oral dosage forms can be inefficient and have been known to produce a large amount of undesired product. With the progressing trend of achieving carbon neutrality, there is an impetus to increase the energy efficiency of these manufacturing processes while maintaining the critical quality attributes of the product. One of the important steps in downstream pharmaceutical manufacturing is wet granulation, and within that, twin screw granulation (TSG) is a popular continuous manufacturing technique. In this study, the energy efficiency of the TSG process was maximized by combining a long-term memory (LSTM) model with an optimization algorithm. The LSTM model was trained on time-series process data obtained from the TSG experimental runs. The optimization process, with the objective of maximizing energy efficiency, was performed using a stochastic optimization algorithm, and constraints were enforced on the process parameter design space. Experimental runs at the optimal process parameters were conducted on the TSG equipment with updates occurring at predefined intervals depending on the optimization scenarios. The purpose of these experimental runs was to validate the capability of increasing the overall process energy efficiency when operating at the optimized process parameters. A maximum increase of 27% was obtained between two tested optimization scenarios while maintaining the yield of the granules at the end of the twin-screw granulation process.

“Fabrication of pellets via extrusion-spheronization for engineered delivery of Famotidine through specialized straws for Paediatrics”

A simple and efficient drug delivery device was designed, viz. specialized straw comprising of famotidine-loaded fast disintegrating pellets. Pediatric dosage forms are designed and developed considering the palatability in children of all ages. This specialized straw was intended for pediatrics presenting with dysphagia or associated symptoms. The pellets were formulated using an extruder spheronization technique incorporated with Kyron T-314 as a super disintegrant. These pellets were characterized for their micromeritic properties, disintegration, and in vitro drug release. The specialized straw was evaluated for various parameters like flow rate of water siphoned through the straw and solvation volume. Pellets were found to have excellent flow properties, disintegration time was found to be 25-30s, and dissolution studies showed 96.1% drug release in 45min. In vitro flow rate was determined to simulate sipping action through this specialized straw. The results indicated that water flowing through the hollow straw at the rate of 13.8±1.3 mLs-1, when tested in prefilled specialized straw, 6.3±1.1 mLs-1 flow rate was observed to be sufficient to dissolve the pellets. Finally, the fast-disintegrating pellets demonstrated excellent in vitro performance and relative ease of manufacturing as compared to other solid dosage forms. Furthermore, the developed specialized straw can be used as a convenient and attractive drug delivery device for pediatrics.

Modern approaches to assessing the quality of orally disintegrating tablets

Orally disintegrating tablets (ODTs) are the preferred and accepted solid dosage forms by patients. These tablets disintegrate in the oral cavity within a short period, providing an advantage for individuals who have difficulty swallowing. Quality control of ODTs can be achieved through measures such as friability, porosity, hardness, wetting time, water absorption capacity, in vitro disintegration test, and dissolution test. This article summarizes the advantages and in vitro quality control tests of orally disintegrating tablets.

Comparison of Co-Processed Superdisintegrants with Superdisintegrants in Drug Release for Palatable Fast Disintegrating Oral Films of Metolazone

The present study was aimed to compare co-proceesed superdisentigrant with superdisentigrants in drug release and formulate a palatable fast disintegrating oral films of metolazone and compare with standard market solid oral dosage forms. The drug was incorporated as solid dispersion to mask the bitter taste of the drug with different polymers in different ratios (PEG 4000 & Poloxomer 407) and was assessed for its taste. Metalazone with Poloxomer 407 (M-SD 5) in the ratio of 1:2 was better masked. The films were prepared by solvent casting method. HPMC E15 & Pullulan were chosen as the film forming polymers and sodium starch glycolate and crosscaramellose sodium were chosen as superdisentigrant for formulation. Pullulan (80mg) and crosscaramellose sodium (0.6%) showed the highest % drug release (99.49±0.15 within 15 min.). Therefore, this composition was chosen to prepare the film having co-processed superdisintegrants (SSG+CCS in 1:1) MF-10. MF-10 showed better disintegration (10 sec) and dissolution rate (99.12% drug release within 10 minutes.) when compared with the best formulation of superdisintigrant. All the evaluations of the optimized formulation were found to be satisfactory and within limits. MF-10 was subjected to stability studies and compared with marketed oral formulation and was found to be satisfactory.
 Keywords: Metolazone, Fast disintegrating oral films (FDOFs), patient compliance, taste mask, rapidly disintegrate, co-processed superdisintegrants.