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Orodispersible films (ODFs) have served as an emerging platform for the delivery of drugs in a convenient way. They have numerous advantages, the significant one is simplicity of administration for special populations such as pediatric and geriatric as well as patients with swallowing difficulty. Besides, the advantages include accurate dosing and fast action. The ODFs are efficiently designed with detailed knowledge of drug and polymers as well as a suitable selection of method. Many conventional and advance formulation strategies have been used for the development of ODFs. The biopharmaceutical concerns of active pharmaceutical ingredients (APIs) are given in this review in light of the fact that ODFs can be utilized to increase the bioavailability of APIs. The basic critical issues such as good mechanical properties, water solubility of the API and taste masking are very important to be considered during the development of ODFs. The knowledge of critical quality concerns of ODFs will be helpful in the future development of ODF. As ODFs remain in the mouth until complete degradation, taste, texture and mouth-feel are the qualities that in all respects liable for acceptability of the patient. An assortment of packaging choices is also accessible for ODFs. This review focuses on the different critical concerns of ODF related to composition, bio-pharmaceutical, manufacturing, quality tests, packaging and acceptability. Additionally, potential barriers in the ODFs development are discussed in details. Therefore, this review is an informative bundle of ODFs concerns from the product development stage to the end-user acceptability.

Microencapsulation of food ingredients such as flavors, vitamins, minerals, essential oils, carotenoids, salts, or enzymes requires stabilization in the environment in which they are placed. Although any food-grade coating material can be conceptually used as a candidate for the microcapsule shell material, most commercial microcapsules produced to date utilize a relatively small number of different shell materials. This is because shell materials for pharmaceutical, food, and personal care products are limited to materials that are approved. Selection of microencapsulated food ingredients requires a careful balance of physical and chemical properties, shelf-life stability, processing of ingredients, and regulatory guidelines. In this chapter, the selection of the matrix material for microencapsulation is classified by the impact that it makes for a particular application. For example, using shelf stability as a criterion, materials are classified by the governing physical property to provide protection against oxygen, pressure, heat, pH, light, heavy metals, and water. Likewise, other applications such as the use of microcapsules in relation to release such as, taste masking, triggered release, color masking, color alteration, and enhanced processability are discussed.

The aim of this study was to develop a pediatric oral preparation for ibuprofen.Ibuprofen is widely used for defervescence in children, but medication compliance is poor due to its bitter taste. Dr...

Common cold is the most frequently recurring disease in the world and is a leading cause of doctor visits and missed days from school and work. Cold reliever medicated chewing gum (MCG) will be a definitive patient acceptable solution for this condition. Dextromethorphan hydrobromide and guaifenesin will be easily released from chewing gum into the salivary fluid within few minutes of chewing and can be easily permeated from oral mucosa by the pressure created by the chewing action and absorbed to a larger extent into the systemic circulation. Therefore, ultimately patients will get quick relief from symptoms of common cold with greater compliance compared to other conventional dosage forms. This study mainly focuses on taste masking of dextromethorphan hydrobromide and guaifenesin with Kyron T-114, its formulation development in the MCG form and its quality and performance evaluation with the study of potential factors affecting drug release by 32 full factorial experimental design. Formulation ingredients, such as elastomers, softeners, bulking agents, play an important role in the feel of the final product and its consistency; while sweeteners and flavours play a very essential character in its sensory properties. Inter individual variation in chewing frequency and chewing intensity is the main factor which affects release of active ingredient from MCG; while salivary dilution and involuntary swallowing are main reasons for variability in the absorption site, i.e., either from buccal mucosa or from gastrointestinal tract.

Paracetamol is a common antipyretic and analgesic medicine used in childhood illness by parents and physicians worldwide. Paracetamol has a bitter taste that is considered as a significant barrier for drug administration. This study aimed to develop an oral dosage form that is palatable and easy to swallow by pediatric patients as well as to overcome the shortcomings of liquid formulations.The paracetamol was encapsulated in beads, which were prepared mainly from alginate and chitosan through electrospray technique. The paracetamol beads were sprinkled on the instant jelly prepared from glycine, ι-carrageenan and calcium lactate gluconate. The paracetamol instant jelly characteristics, in terms of physical appearance, texture, rheology,The paracetamol instant jelly was easily reconstituted in 20 mL of water within 2 min to form jelly with acceptable consistency and texture. The jelly must be ingested within 30 min after reconstitution to avoid the bitter taste. The palatability assessment carried out on 12 human subjects established the similar palatability and texture of the paracetamol instant jelly dosage comparable to the commercial paracetamol suspension and was found to be even better in overcoming the aftertaste of paracetamol.Such findings indicate that paracetamol instant jelly will compensate for the use of sweetening and flavoring agents as well as develop pediatric dosage forms with limited undesired excipients.

Background Among all available dosage form, tablet is most widely used because of its stability and patient acceptability. The better aesthetic quality like color, texture, mouth feel, and taste masking depended on film and sugar coatings, so the coating is an important part in the formulation of the tablet. The present work aims to comprehensively review the formulation, characterization, and challenges in the development of Tablet in Tablet dosage form. Main text Film and sugar coatings have the number of disadvantages; most important one is the utilization of aqueous or organic solvent that leads to toxicity. To overcome this problem in the year 1896, Noyes firstly introduced the compression coating or Tablet in Tablet technique. In the development of Tablet in Tablet dosage form, substantial attention among researchers and various research reports and patents inputs can be found in the literature. Also, we focused on the recent advancements in techniques like one-step dry-coating (OSDrC®) for manufacturing Tablet in Tablet dosage form. Conclusion The current review gathered information on the latest patent, formulation, advantages, and disadvantages of Tablet in Tablet or compression coating. The review also elaborates on the importance of Tablet in Tablet techniques in the development of a modified release system. Graphical abstract

INTRODUCTION Child appropriate dosage forms are indispensable in modern medicine and are a prerequisite for successful pediatric drug therapy. For years, experts have called for a paradigm shift, from liquid dosage forms to novel oral solid dosage forms. This review aims to shed light on recent developments in Orodispersible tablets (ODTs) and mini-tablets (ODMTs). AREAS COVERED This review focuses on the presentation and critical discussion of current challenges as well as recent advances in ODTs for pediatric drug delivery. Highlighted aspects are the evidence for acceptability by children, e.g. in comparison to other dosage forms, and limitations given by tablet size at different ages, as well as advances in special ODT formulations (taste masking, modified release, enabling formulations). EXPERT OPINION It is the authors' belief that OD(M)Ts have significant potential as dosage forms in pediatric therapy that has not yet been fully exploited. The reasons for this are, first, that the number of direct acceptance studies is extremely low and the resulting knowledge is therefore rather anecdotal. Despite the high relevance, there seems to be reluctance both in the therapeutic use and conduction of respective studies in children. However, if one combines the knowledge from the few existing studies, surveys, and from approved products, it becomes apparent that so far there is no evidence on limitations of the use of ODTs in pediatric patients.

Palatability is amongst the most important determinants of whether or not a child will take a medicine. In order to increase concordance with treatment regimens it is often necessary to utilise a range of formulation techniques to improve the palatability of medicines. These can include selecting a different molecule or version of a molecule (such as a different polymorph or salt form), various taste masking techniques and/or the inclusion of flavours and sweeteners. In order to be able to understand the taste of the Active Pharmaceutical Ingredient (API) and to validate the formulation approach used, it is necessary to be able to use the most reliable taste evaluation method possible. Multiple in vivo and in vitro methods exist nowadays or are proposed in the literature but are often little understood by the pharmaceutical product development community. In particular, different methods may be more relevant at different stages of product development. The aim of this article is to propose a tool to guide the selection of the most appropriate method for the desired evaluation. A spreadsheet-based tool is proposed that is designed to allow the systematic assessment of the applicability of any taste assessment technique existing or new to the users proposed application. A series of criteria are defined that will allow the user to assess the analytical, usability and availability factors for the technique that is being considered. Such a systematic review will help the user to understand the benefits and risks of using each methodology for that application. The use of the tool is illustrated based on currently available data and literature. As new/existing methods are developed/improved, the outcomes of the tool may change.

Orodispersible tablet (ODT) provides rapid disintegration in the oral cavity. ODT improves the efficacy of using medicines especially in term of compliance in a patient with dysphagia. The major challenge of ODT is a bitter taste of active pharmaceutical ingredient (API); they can lead the patients to refuse medication. This study focused on the developing of the orodispersible disc (ODD) with a taste masking property by preparation of API particle that was taste-masked by polymers. The co-precipitation technique was used for the taste masking. Acetaminophen (APAP) taste-masked particles prepared with different grades of crospovidone were investigated for the taste-masking property. Kollidon® CL-SF exhibited the lowest drug release. An increasing amount of Kollidon® CL-SF caused increasing of APAP release. Particles consisted of APAP:crospovidone at ratio 3:1 showed the lowest drug release. It was probably due to the complexation which was shown by the FT-IR and DSC. Taste-masked particles were compressed as ODD by a hydraulic press machine. The disintegrating time of ODD was at the range of 12.62-17.35 s. The dissolution of ODD was focused on the taste-masking zone (drug release in 1 min). The ODD with ratio 3:1 particle (APAP: Kollidon® CL-SF) showed the highest taste-masking performance, the lowest drug release. All disc formulations completely released APAP after 30 min. Therefore, the preparation of ODD contains taste-masked particles was promising to improve patient compliance of bitter APIs.

Orodispersible films (ODFs) are ultra-thin, stamp-sized, elegant, portable and patient-centric pharmaceutical dosage forms that do not need water to be ingested. They are particularly useful for paediatric and geriatric patient populations with special needs such as dysphagia, Parkinson's disease, and oral cancer. Accordingly, they hold tremendous potential in gaining patient compliance, convenience and pharmacotherapy. In the present review, conception and evolution of ODFs as a product and its technology are discussed. The review continues by providing overview about the potential of ODFs as carriers for delivering drugs, herbal extracts, probiotics and vaccines. Besides, strategies employed in drug cargo loading, taste masking of bitter drugs and enhancing drug stability are discussed. Finally, the review concludes by providing a brief overview about quality by design (QbD) principles in development of ODFs.

Oral route, the most widely accepted route for drug applications, has some drawbacks such as difficulty in swallowing and the lack of utilization without water. Therefore, orally disintegrating tablets (ODT), or so-called fast disintegrating tablets (FDT), have been developed, by which the dispersion of the tablet in the oral cavity provides the release of drug and its pre-gastric absorption with no need for water and swallowing. The development of such a formulation is possible using different methods, most importantly using granulation. Wet granulation, dry granulation, and melt granulation are counted as the most important methods in this regard. In all of these methods, a disintegrant or superdisintegrant, a lubricant, in some cases a permeabilizing agent, a sweetener, and finally a flavoring agent are utilized to provide a fast disintegration process for accomplishing the patient compliances. In this chapter, a brief explanation of the desired properties of ODTs and the needs for their development is followed by their production technologies with special emphasis on granulation. Furthermore, the challenges in preparation of ODTs such as taste masking and affording fast disintegration without producing highly fragile tablets are discussed in detail. The chapter is finalized with the characterization methods of ODTs.

The current availability of dosage forms designed specifically for children is limited, constituting common practice the use of unlicensed or off-labeled medicines and extemporaneous preparations. Swallowing difficulties and taste aversion are the primary reasons for medicine rejection; therefore, enhancing palatability and ease of administration are the most common approaches adopted to overcome these issues.A search of patents was performed for pediatric dosage forms and devices. The review aims to provide an overview on new formulation approaches and technologies adopted to develop pediatric-friendly dosage forms and devices, as well as on the regulatory efforts aiming to support the pediatrics market.Children deserve medicines of the same efficacy, quality and safety as adults. The present review highlights the momentum developed by pharmaceutical industries in the field of pediatrics, since more than 60 patents have been published in the last 5 years. An increasing interest, especially in mini-tablets, orodispersible, and chewable dosage forms, as well as on excipients and methods, to achieve sufficient taste-masking was identified, recognizing also the need for coordinated research networks and sustainable collaborations across the public and private sectors to provide better medicines for children.

This review highlights the recent formulation advances (different methods of preparation involving various novel approaches) that have been advancing the use of ODT as a popular dosage form. Furthermore, the important characteristics of ODTs that are required for patient compliance and appropriate therapeutic benefit are discussed. In addition to conventional ODTs, ODTs formulated for controlled release of pharmaceuticals and taste masking are also discussed.

Acceptable palatability of an oral dosage form is crucial to patient compliance. Excipients can be utilised within a formulation to mask the bitterness of a drug. One such category is the bitter-blockers. This term is used inconsistently within the literature and has historically been used to describe any additive which alters the taste of an unpleasant compound. This review defines a bitter-blocker as a compound which interacts with the molecular pathway of bitterness at a taste-cell level and compiles data obtained from publication screening of such compounds. Here, a novel scoring system is created to assess their potential utility in a medicinal product using factors such as usability, safety, efficacy and quality of evidence to understand their taste-masking ability. Sodium acetate, sodium gluconate and adenosine 5'monophophate each have a good usability and safety profile and are generally regarded as safe and have shown evidence of bitter-blocking in human sensory panels. These compounds could offer a much needed option to taste-mask particularly aversive medicines where traditional methods alone are insufficient.

Patients suffering from dysphagia have trouble in swallowing conventional oral dosage forms and there is also risk of choking, which may cause patient noncompliance. This study aimed to develop an orodispersible film (ODF) containing cefixime trihydrate (CFX) to cope with the above-mentioned problems as well as to enhance water solubility and masking the bitter taste of the drug. The freeze-drying and kneading methods were used for the formation of inclusion complexes. The physicochemical evaluation revealed that T7 was the best film for the incorporation of pure drug and inclusion complexes. Films were further characterized for physical and mechanical properties. Drug content, dissolving time of the film and drug release tests were performed. In vivo taste and disintegration time studies were also conducted in healthy human volunteers. FTIR spectra of the individual ingredients and prepared formulations have confirmed the chemical compatibilities of the ingredients. The solubility of CFX was increased by complexation with β-CD and optimized freeze-dried inclusion complex (FD1) was selected for the formation of ODF. C4 was selected as an optimized film for the delivery of CFX as this film has released 95.52% drug at the end of 10 min. Dissolution kinetics of FD1 showed that it followed zero-order kinetics while drug release from films, exhibits first-order kinetics; however, both showed non-Fickian transport. In vivo taste evaluation revealed that taste was masked by inclusion complexation with β-CD. However, selected ingredients and employed methodology enabled to formulate film, capable of delivering taste-masked CFX with improved solubility and better patient compliance.

An orally disintegrating tablet is a novel formulation that dissolves in the saliva within a few seconds and without requiring of drinking additional water. This dosage form is a powerful way to deliver active drugs ingredients because it has many advantages. Many studies have compared this form of tablet with the ordinary forms in vitro and in vivo and found that orally disintegrating tablets have superior patient compliance and drug solubility. However, there are some criteria for the active pharmaceutical ingredients to prepare tablets as fast dissolve forms. There are several ways to prepare this dosage form and each method has its pros and cons. Technologies of preparation and various examples of orally disintegrating tablet available in the market using different preparing procedures are presented in this review. Taste masking is required form some active pharmaceutical ingredients to be formed as orally disintegrating tablets. In vitro evaluation and quality control measures of orally disintegrating tablet is also discussed in this review.

Pharmaceutical Co-crystals are not new, they have gained much attention since the last decade among scientists and pharmaceutical industry. Pharmaceutical co-crystals are multicomponent systems composed of two or more molecules and held together by non-covalent interactions. The development of pharmaceutical co-crystals, a new solid crystalline form, offer superior physico-chemical properties (such as melting point, stability, solubility, permeability, bioavailability, taste masking, etc.) without altering the pharmacological properties. Recently, with the upsurge in the growth of Pharmaceutical co-crystals, the major concern is over the regulatory status of co-crystals. With the new guidelines from United States Food and Drug Administration (USFDA) and European Medicines Agency (EMA), the status has become even more complicated due to significantly different opinions. This review highlights whether co-crystals fulfil the requirements for the grant of a patent or not and how cocrystals are going to affect the present scenario of pharmaceuticals.

Undesirable taste is an important problem for patient compliance. Several oral pharmaceuticals and bulking agents have disagreeable and bitter-tasting components. The Bitter taste characteristics found in such systems have been eliminated or minimized by the development of numerous formulations with improved performance and acceptability especially in children and elderly patient. This review is mainly concerned with the bitter-masking techniques published in peer-reviewed journals and will shed light on different methods of masking undesirable taste of the drugs, and their pharmaceutical applications. Hence, nearly no reference will be made to the techniques published as patent applications.

International audience; For the last 40 years, praziquantel has been the standard treatment for schistosomiasis, a neglected parasitic disease affecting more than 250 million people worldwide. However, there is no suitable paediatric formulation on the market, leading to off-label use and the splitting of commercial tablets for adults. In this study, we use a recently available technology, direct powder extrusion (DPE) three-dimensional printing (3DP), to prepare paediatric Printlets™ (3D printed tablets) of amorphous solid dispersions of praziquantel with Kollidon® VA 64 and surfactants (Span™ 20 or Kolliphor® SLS). Printlets were successfully printed from both pellets and powders obtained from extrudates by hot melt extrusion (HME). In vitro dissolution studies showed a greater than four-fold increase in praziquantel release, due to the formation of amorphous solid dispersions. In vitro palatability data indicated that the printlets were in the range of praziquantel tolerability, highlighting the taste masking capabilities of this technology without the need for additional taste masking excipients. This work has demonstrated the possibility of 3D printing tablets using pellets or powder forms obtained by HME, avoiding the use of filaments in fused deposition modelling 3DP. Moreover, the main formulation hurdles of praziquantel, such as low drug solubility, inadequate taste, and high and variable dose requirements, can be overcome using this technology.

Drug therapy for children is one of the cornerstone developments that have sharply reduced childhood mortality. Despite this, many challenges remain in ensuring that children receive safe and effective drug therapy. There are unique issues in treating children with oral medication relating to development, existing formulations and medication acceptability. Medication acceptability in children is complex relating to a wide range of factors, including drug palatability. Over the past decade there has been an increasing interest in and research as to how to improve and enhance child-specific drug formulations including the development of specific instruments for assessing drug palatability in children and new approaches to teaching medication literacy to families. Approaches to enhancing drug acceptability have also included organoleptic (taste masking) strategies as well as the creation of a number of innovative taste-blocking strategies and new technologies for formulation preparation. Polymer coating, microencapsulation and heat melt technologies have resulted in drug formulations that are now being assessed in children while soft melt and gel formulations are now commonly used. Mini-tablets offer the potential of using solid delivery systems in even very young infants. This work has resulted in a number of highly promising developments that are being evaluated for clinical use as well as providing insights into new directions in pursuit of the common goal of effective and safe drug therapy for children. On-going challenges include the need for drug regulatory agencies to work closely with drug regulatory agencies in facilitating innovation in formulation design and approval.

Orally disintegrating tablets and oral lyophilisates are novel attractive dosage forms that disintegrate or dissolve in the buccal cavity within seconds without necessity of drinking. The major limitation in designing of these dosage forms is unpleasant taste of the drug substance. Cetirizine dihydrochloride is a H1-antihistamine substance indicated for the treatment of allergy. It is characterized by extremely bitter taste, therefore in order to deliver cetirizine dihydrochloride using orodispersible formulations, effective taste-masking is required. The aim of this study was to investigate whether microparticles containing cetirizine dihydrochloride could be successfully used to formulate orally disintegrating tablets by direct compression method and oral lyophilisates by freeze-drying process. Taste masking of cetirizine dihydrochloride was achieved by the spray-drying technique using Eudragit® E PO as the drug agent carrier. Based on the preliminary studies, optimal compositions of microparticles, tablets and lyophilisates were chosen. Obtained dosage forms were characterized for drug content, disintegration time and mechanical properties. In order to determine whether the microparticles subjected to direct compression and freeze-drying process effectively mask the bitter taste of cetirizine dihydrochloride, the in vivo and in vitro evaluation was performed. The results showed that designed formulates with microparticles containing cetirizine dihydrochloride were characterized by appropriate mechanical properties, uniformity of weight and thickness, short disintegration time, and the uniform content of the drug substance. Taste-masking assessment performed by three independent methods (e-tongue evaluation, human test panel and the in vitro drug release) revealed that microparticles with Eudragit® E PO are effective taste – masking carriers of cetirizine dihydrochloride and might be used to formulate orally disintegrating tablets and oral lyophilisates. Keywords: Orally disintegrating tablets, Oral lyophilisates, Cetirizine dihydrochloride, Taste masking, E-tongue

Objectives Prednisone is a widely used anti-inflammatory for a variety of conditions. While oral liquid formulations of prednisone enable weight-based dosing, children frequently find them to be objectionable due to bitter taste. This limitation of prednisone can adversely impact patient acceptance and may result in non-compliance. Efforts to mask flavours often result in poorly controlled, heterogeneous particle distributions and can provide ineffective taste masking. The present work utilized a novel drug delivery technology developed by Orbis Biosciences, Inc., to create an oral taste-masked formulation of prednisone. Methods The study examined the palatability of Orbis’ microsphere prednisone formulation in healthy young adults (n = 24). Four test articles were used in the study including a reference formulation (Roxanne Laboratories), a control and the test formulation (Orbis) prepared in two different ways. Study participants were randomized in a crossover design. Key findings Results indicated that the test prednisone formulation was indistinguishable from the control, and both were preferable to the reference formulation in every category of palatability assessed using a validated 9-point Hedonic Scale. The data also suggested that preparing the microsphere suspension immediately before administration results in the most ideal palatability properties. Conclusions In conclusion, the novel microsphere formulation technology was effective in taste-masking prednisone.

Hot Melt Extrusion (HME) technology is a widely used for manufacturing process in the plastic and pharmaceutical industries and is an efficient and simple for the production of a solid dispersion. This technique is an environmental friendly, continuous process that does not use solvents. It is time and cost efficient and can be easily scaled up. In addition, HME may be used in conjunction with other technologies to effectively increase the solubility and dissolution rate of poorly water-soluble drugs. Numerous research papers on the progress of HME technology in the pharmaceutical industry have been written, and products manufactured using HME have been approved by the FDA. However, there are some drawbacks to the products manufactured using through HME. These are related to the high energy input coming from the applied shear forces and high temperature, which could lead to drug or polymer degradation and thus significantly impact the product quality. Despite these disadvantages, HME has been employed in various advanced applications, such as taste masking and targeted drug delivery. This review article focuses on advances in HME technology, which include improvement in the weaknesses of HME, patient-centric formulations, and the outlook for uses such as formulation development.

Hydroxychloroquine sulfate (HCQ) is a quinoline used for the prevention and treatment of uncomplicated malaria, lupus erythematosus, and rheumatoid arthritis. For each indication, HCQ is an option for treatment of pediatric and juvenile patients on a weight basis; however, no tailored pediatric product is available on the market. Preliminary research confirmed that a slightly buffered, ion-pairing system significantly reduces the bitterness of HCQ, suggesting a high likelihood that a pediatric taste-masking system could be interwoven into an adult immediate-release formulation allowing the creation of a palatable suspension with water using common excipients. Because HCQ is a Biopharmaceutics Classification System Class 1 drug, the pharmacokinetics for an adult immediate-release formulation would not be altered by embeding a taste-masking system. Embedding the taste-masking and suspension agents within the adult tablet formulation would remove the need for aqueous-based vehicles and simplify the creation of a water-based suspension formulation to support improved compliance, dosing accuracy, and health outcomes in pediatric patients who are weight-base dosed with HCQ.

Pediatric and geriatric patients experience swallowing difficulties for traditional oral dosage forms, such as tablets. Further, microbial contamination, chemical stability, unpleasant taste and swallowing large volumes of fluids have led to low therapeutic efficacy and patient noncompliance. The emergence of oral thin films has resulted in dramatic improvements in compliance and drug therapy outcomes in pediatric and geriatric patients. Oral thin films do not require water for administration, are readily hydrated upon contact with saliva, adhere to the mucosa and disintegrate ideally under 1 min. This article provides an overview of oral thin films, modern trends in their formulation and characterization, available commercial products, information to fill knowledge gaps and future potential and economic prospects of oral thin film technology, with emphasis on their use in the pediatric and geriatric patient groups.

In pediatrics, it is crucial to ameliorate the unpleasant taste of oral pharmaceutical formulations in order to facilitate patient compliance. Scientists' attempt to develop modern products for children is included among the new trends in pharmaceutical technology. Designing the preparation procedures and selecting the age-appropriate dosage form should be based on a benefit-risk approach, taking into account safety, efficacy, ease of use and accessibility to the patient. Part of this process should examine the necessity for taste masking, considering organoleptic and physicochemical properties of the active pharmaceutical ingredient. This research describes the incorporation of metoclopramide hydrochloride in the form of a soft candy (jelly) containing pomegranate juice. The low cost excipients and the ease of preparation are such characteristics that qualify the proposed technique as one of the alternative methods for modern drug formulations. At the same time, metoclopramide is quantitatively determined by developing a reverse phase HPLC method. The method is accurate (%RSD = 2.63, %mean recovery = 100.75) and can be used for routine analysis. The stability of metoclopramide was satisfactory after 6 months of storage (recovery 103.43%). Dissolution of the drug exceeded 92%. The proposed formulation enclosing metoclopramide in a jelly is modern, palatable and can be administered to children.

The global market of pharmaceuticals has witnessed a new revolution recently in the form of threedimensional printing (3D) technology. 3D printing has its existence since the 1980s that uses a 3D printer to manufacture the different dosage forms through computer-aided drug design technology. The need for 3D printing is due to numerous advantages like personalized medicine, tailored doses, rapid disintegration in case of SLS technique, incorporation of high doses and taste masking capacity. The different techniques used in 3D printing are Powder based (PB), Semi-solid extrusion (EXT), Fused deposition modeling (FDM), Stereolithographic (SLA) and Selective laser sintering (SLS) 3D printing. However, from the latest reports of association of pharmaceutical 3D printing technology, it is evidenced that this technology is still in its infancy and its potential is yet to be fully explored. The present review includes sections for introduction and scope of 3D printing, personalized medicines and their approaches, historical aspects, research milestones, and various 3D printing techniques.

The purpose of this review is to discuss the advantages and limitations of taste sensors in the evaluation of the taste of palatability of different oral dosage forms. First, we consider some ways in which the palatability of various pharmaceutical formulations including orally disintegrating tablets (ODTs) are tested using two different taste sensors. Second, we focus on the evaluation of palatability of ODTs. We compare the usefulness of three pieces of apparatus for estimating the disintegration time of ODTs. Finally, we compare the characteristics of the two taste sensors in the evaluation of palatability of various kinds of drug formulations.

The European Paediatric Formulation Initiative (EuPFI), founded in 2007, aims to promote and facilitate the preparation of better and safe medicines for children through linking research and information dissemination. It brings together the capabilities of the industry, academics, hospitals, and regulators within a common platform in order to scope the solid understanding of the major issues, which will underpin the progress towards the future of paediatric medicines we want.The EuPFI was formed in parallel to the adoption of regulations within the EU and USA and has served as a community that drives research and dissemination through publications and the organisation of annual conferences. The membership and reach of this group have grown since its inception in 2007 and continue to develop and evolve to meet the continuing needs and ambitions of research into and development of age appropriate medicines. Five diverse workstreams (age-appropriate medicines, Biopharmaceutics, Administration Devices, Excipients and Taste Assessment & Taste Masking (TATM)) direct specific workpackages on behalf of the EuPFI. Furthermore, EuPFI interacts with multiple diverse professional groups across the globe to ensure efficient working in the area of paediatric medicines. Strong commitment and active involvement of all EuPFI stakeholders have proved to be vital to effectively address knowledge gaps related to paediatric medicines, discuss potential areas for further research and identify issues that need more attention and analysis in the future.

The development of medicines designed for children can be challenging since this distinct patient population requires specific needs. A formulation designed for paediatric patients must consider the following aspects: patient population variability; dose flexibility; route of administration; patient compliance; drug and excipient tolerability. The purpose of this Special Issue entitled “Paediatric Formulation: Design and Development” is to provide an update on both state-of-the-art methodology and operational challenges in the design and development of paediatric formulations. It aims at re-evaluating what is needed for more progress in the design and development of age-appropriate treatments for paediatric diseases, focusing on: formulation development; drug delivery design; efficacy, safety, and tolerability of drugs and excipients. This editorial, briefly, summarizes the objects of nine original research and review papers published in this Special Issue.

Oral administration is the most accepted and favored route as various side effects such as fear, pain and risk of infections can be avoided resulting in a comparatively high patient compliance. However, from the industrial point of view the development of oral delivery systems is still challenging as various drugs are poorly soluble as well as slightly permeable leading to low bioavailability. As self-emulsifying drug delivery systems are able to incorporate both hydrophobic and hydrophilic drugs, these carrier systems have received more and more attention within the last years. Based on the broad range of currently available excipients, this review provides a kind of guideline for the selection of excipients useful to improve bioavailability of the drug on the one hand. As the regulatory status of potential excipients are highly important to introduce the formulation on the market, the review is focused on the other hand on excipients listed in the IIG database of the FDA by taking their corresponding maximum concentration into account. Furthermore, the issue of oral sensation and taste masking is discussed useful for the development of intraoral SEDDS.

Many drugs are bitter and overcoming this bitter taste is a major barrier in developing a successful product, especially for pediatric patients. Approaches to mask taste include changing taste perception, creating a physical barrier to separate the drug from interacting with taste buds, and changing drug solubility. This review is focused on polymers and the different ways these materials are used to achieve taste masking. Attention is given to systems that are easily swallowed, as swallowability is another concern in developing palatable products for pediatrics. Variables that should be considered when selecting a taste-masking approach are also presented.

The oral route of drug administration is mostly preferred by paediatric and geriatric patients. Patient non-compliance due to poor taste and swallowing problems are major issues in paediatric and geriatric drug therapy. Lack of age-appropriate formulations, inadequate labelling instructions, non-compatible and non-palatable medicines are the main reasons for medication errors in paediatric patients. This review mainly highlights major issues of paediatric and geriatric drug therapy and provides the design of oral flexible formulations as an alternative formulation design for age appropriate formulation development. Development of solid oral flexible formulations as an alternative to existing marketed formulations such as conventional tablets, orally disintegrating tablets, chewable and dispersible tablets for paediatric and geriatrics patients is described. Details about drug properties, excipient selection and taste masking approaches were described. The need for bioavailability and bioequivalence studies for flexible formulations also described. Development of flexible formulations as an alternative to marketed different formulations of the same drug would reduce the cost of the formulation for patients particularly developing countries where accessibility to various types of formulations is less. Flexible tablet formulations can be conveniently used by the patients as orally swallowable, orally disintegrating, chewable and as dispersible tablets. Sprinkle formulations such as pellets, granules packed in capsules or sachets can be conveniently used by paediatric and geriatric patients. Properly designed and developed flexible formulations for new chemical entities and off-patent drugs are need of the hour to provide better treatment to varying age groups of paediatrics and geriatrics.

There is a growing number of children worldwide accessing second-line anti-tuberculosis drugs for multidrug-resistant tuberculosis (TB); however, there are very few child-friendly formulations. For paediatric use, dispersible tablets offer distinct advantages over liquid formulations and other approaches. This is particularly relevant for TB, where stability, long shelf-life and reduced manufacturing, transport and storage costs are all critical to ensuring that drugs are accessible and affordable. In addition, fixed-dose combinations that reduce the pill burden and provide adequate taste masking may promote long-term adherence to anti-tuberculosis treatment and prevention regimens likely to last many months in children. Partial adherence may result in treatment failure and the further selection and spread of resistant mycobacteria. Unfortunately, no second-line TB paediatric drugs exist in dispersible formulations. We discuss here the main obstacles to developing such tablets and present strategies for overcoming them. We also advocate for timely anticipation of paediatric use when new TB drugs are being developed, and for the development of child-friendly anti-tuberculosis formulations in general.

The first aim of the present study was to evaluate the bioavailability of ibuprofen dispersed in a novel soft chewable formulation compared with a traditional ibuprofen tablet; its second was to map the quality of taste masking and patient product satisfaction. In a phase 1, single-center, open-label, randomized, crossover study, healthy subjects received a soft-chew formulation or a hard tablet (reference), both containing 100 mg ibuprofen. Serial blood samples were collected over 24 hours to assess ibuprofen bioavailability. Taste and satisfaction after chewing the novel formulation 3 or 8 times were evaluated with a questionnaire. The soft-chew formulation showed comparable bioavailability to the reference tablet. The highest peak plasma concentration was observed after 3 chews, and the relative bioavailability was approximately 8% higher compared to 8 chews. The overall flavor was well appreciated, and chewing 3 times was significantly preferred (P = .043) over chewing 8 times. Soft chewable drug formulations may improve compliance and potentially benefit several subpopulations who experience dysphagia. © 2017, The Authors. Clinical Pharmacology in Drug Development published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License.

Introduction: Orally disintegrating tablets (ODTs) provide an important treatment option for pediatric, geriatric and psychiatric patients. In our previous study, we have performed the initial studies for the formulation development and characterization of new ODT formulations containing a bitter taste drug, mirtazapine, coated with 6% (w/w) Eudragit® E-100 (first group of formulations, FGF) without taste evaluation. In present study, coating ratio of the drug was increased to 8% (w/w) (second group of formulations, SGF) to examine the effect of increased coating ratio of drug on in vitro characterization of the formulations including in vitro taste masking study. Materials and methods: Coacervation technique using Eudragit® E-100 was employed to obtain taste-masked mirtazapine granules. FGF and SGF were compared to original product (Remeron SolTab, an antidepressant drug which produced by pellet technology) in terms of in vitro permeability, in vitro taste masking efficiency which was performed by dissolution studies in salivary medium and dissolution stability. Also, the other tablet characteristics (such as diameter, thickness) of SGF were examined. Results and discussion: The disintegration time of the SGF were found as A1 ® E-100), but all of the formulations dissolved under 30 seconds and friability values were less than 1%. In vitro taste masking efficiency studies demonstrated that C2 formulation (in FGF) had the most similar dissolution profile to Remeron SolTab. Conclusions: According to these findings, B2 or C2 (with citric acid or sodium bicarbonate, respectively, with 6% Eudragit® E-100) formulations could be promising alternatives to Remeron SolTab.

Taste is the maximum valuable factor within the ca Taste is the maximum valuable factor within the case of orally drugs administering. Flavor covering is a prerequisite for bitter tablets to better the patient compliance, particularly in the paediatrics and geriatric population. The hassle of the sour taste of drug in pediatric formulations is a completely huge task to the formulators on this gift time. Overlaying is an effective device for the development of the sour taste of medication of patient compliance which sooner or later comes to a decision the commercial achievement of the product. In recent times, two maximum usually software are utilized to conquer the horrific flavor of the drug. The primary software consists of reduction of drug solubility within the saliva and second to modify the potential of the drug to interact with taste receptor. At present various methods are available in the market to masks the unwanted taste of the drugs. Some of them are the mass extrusion strategies and ion trade resins, molecular complexes of drugs with other chemical substances, coating of drug debris, melting method, micro encapsulation by using a formation of inclusion complexes, stable dispersions, prodrugs. USe of orally drugs administering: Flavor covering is a prerequisite for bitter tablets to better the patient compliance, particularly in the paediatrics and geriatric population. The hassle of the sour taste of drug in pediatric formulations is a completely huge task to the formulators on this gift time. Overlaying is an effective device for the development of the sour taste of medication of patient compliance which sooner or later comes to a decision the commercial achievement of the product. In recent times, two maximum usually software are utilized to conquer the horrific flavour of the drug. The primary software consists of reduction of drug solubility within the saliva and second to modify the potential of the drug to interact with taste receptor. At present various methods are available in the market to masks the unwanted taste of the drugs. Some of them are the mass extrusion strategies and ion trade resins, molecular complexes of drugs with other chemical substances, coating of drug debris, melting method, micro-encapsulation by using a formation of inclusion complexes, stable dispersions, prodrugs

The development of paediatric medicines can be challenging since this is a diverse patient population with specific needs. For example, the toxicity of excipients may differ in children compared to adults and children have different taste preferences. Acceptable palatability of oral paediatric medicinal products is of great importance to facilitate patient adherence. This has been recognised by regulatory authorities and so is becoming a key aspect of paediatric pharmaceutical development studies. Many active pharmaceutical ingredients (APIs) have aversive taste characteristics and so it is necessary to utilise taste masking techniques to improve the palatability of paediatric oral formulations. The aim of this review is to provide an overview of different approaches to taste masking APIs in paediatric oral dosage forms, with a focus on the tolerability of excipients used. In addition, where possible, the provision of examples of some marketed products is made.

The aim of present research was to design and evaluate orally disintegrating tablet (ODT) of novel lamotrigine-cyclamate salt. Box-Behnken response surface methodology was selected to design the optimized formulation. The independent factors selected were tablet hardness (X1), disintegrant (X2) and lubricant (X3) levels, and responses chosen were disintegration time (DT, Y1), friability (Y2), T50 (Y3), and T90 (Y4). The tablets were also characterized for drug uniformity by near infrared chemical imaging (NIR-CI) and taste masking evaluation by electronic tongue. All the selected independent variables were statistically (p

Rats have inherent licking behavior and responses to good and aversive tasting stimuli, which are comparable to humans. Taste masking of chewable and orodispersible tablets of an iron EDTA complex salt was evaluated using rat behavioral avoidance model, brief access test. Taste-masked chewable and orodispersible tablets of iron EDTA complex were prepared using various flavors and sweeteners as taste-masking agents. These formulations were presented to rats and their responses were recorded in terms of licking frequency and other avoidance responses. Formulations were also presented to human volunteers and a correlation between responses of humans and rats was tried to be established. Taste responses of rats were found to be similar to those of humans. A high correlation between the taste responses of rats and humans was observed. Evaluation of taste masking using human panels presents several difficulties such as ethical concerns, fatigue and subjectivity. Thus, rat behavioral avoidance model can be considered as a good alternative to taste assessment by human volunteers for further such investigations.

The concept of mouth dissolving tablets known as MDTs has emerged with an objective to improve patient’s compliance. Methods to improve patient’s compliance have always attracted scientists towards the development of fancy oral drug delivery systems. Among them, mouth dissolving drug delivery systems (MDDDS) have obtained an important position in the market by overcoming previously encountered administration problems and contributing to extension of patent life. These dosage forms rapidly disintegrate in contact with saliva even within

The fourth annual European Paediatric Formulation Initiative (EuPFI) conference on Formulating Better Medicines for Children was held on 19–20 September 2012 at the Institute of Molecular Genetics Congress Centre, Prague, Czech Republic. The 2-day conference concentrated on the latest advances, challenges and opportunities for developing medicinal products and administration devices for pediatric use, both from European and US perspectives. It was aimed specifically at providing exposure to emerging practical applications, and for illustrating remedies utilized by pediatric drug-development teams to overcome hurdles faced in developing medicines for pediatric patients. The conference format included plenary talks, focus sessions on each of the EuPFI work streams (extemporaneous preparations, excipients, pediatric administration devices, taste masking and taste assessment, age-appropriate formulations), case studies, soapbox sessions and a parallel poster display. This conference report summarizes the keynote lectures and also gives a flavor of other presentations and posters from the conference.

Novel drug delivery systems, which facilitate swallowing and improve patient adherence due to bitter taste masking of Active Pharmaceutical Ingredient (API), gain an increasing interest in recent years. Usually, studies on the taste of pharmaceutical products are conducted by human taste panel, but it concerns ethical doubts. Electronic tongue is one of the candidate tools allowing for fast, repeatable, and objective analysis of pharmaceuticals. In this work a sensor array composed of cross-selective electrodes was coupled with Principal Component Analysis in order to assess the taste-masking efficiency of the microencapsulated API (cetirizine dihydrohloride) formulated in lyophilisates. The obtained results show that presented electronic tongue can be used for the recognition of the studied pharmaceutical formulations and evaluation of the taste-masking effect.

The purpose of this study is to develop an oral suspension of clindamycin resin complex for the potential use in pediatrics.Several types of Ion exchange resins were screened for their binding efficiency with clindamycin. In order to develop a suspension formulation, several thickening agents, surfactants, sweeting, and flavoring agents were evaluated for their influence on the release of clindamycin from resinate. Rheological studies were also conducted to select the optimum amounts of the suspending agents. The release profiles of clindamycin in SGF and SIF were also evaluated from freshly prepared suspension and from suspension formulation after storage for 1 month at 25 °C and 40 °C. Clindamycin bitterness threshold was determined based on volunteers' evaluation, and taste evaluation was conducted in 12 adult volunteers who evaluated the taste of the optimized suspension against clindamycin solution.Among all resins tested, Amberlite IRP 69 showed the highest binding efficiency to clindamycin. Several excipients were selected into the suspension formulation based on no or minimum influence on the release of clindamycin from the resinate complex. Moreover, xanthan gum was selected as the optimal suspending agent for the suspension. Clindamycin release profiles in SGF or SIF showed 90% release within 30 min from freshly prepared sample. Clindamycin exhibited good stability profiles at 25 °C and 40 °C over 1 month storage. The mean bitterness threshold of clindamycin was 12.5 μg/ml, and taste evaluation study in adults showed sustainable taste improvement for suspension over clindamycin solution.Clindamycin/resin complexation has shown to be an efficient method to mask the taste of clindamycin and was developed into a suspension formulation that can be used in pediatrics.

The multiparticulate drug product concept covering micropellets, pellets, and mini-tablets is presented as a highly feasible approach to present convenient and patient friendly medication for the geriatric population. Improved swallowability and optimized administration regimen going along with defined drug dosage are achievable. Extemporaneous preparation of medicines from standard medication can be avoided going along with improved patient safety. With one multiparticulate pellet, micropellet, or mini-tablet bulk formulation a broad range of final drug products is presentable applying well-established manufacturing technologies at viable cost.

In the last decade the development of orally disintegrating tablets (ODTs) and thin-film platforms has grown enormously in the field of pharmaceutical industry. A wide variety of new masking technologies combined with the aforementioned platforms have been developed in order to mask the taste of bitter active substances and achieve patient compliance. The commercial success and viability of such products requires the development of robust formulations with excellent palatability, disintegration times, physicochemical stability and pharmacokinetic profiles.In this review, emerging taste-masking technologies applied to solid dosage form manufacturing are summarized. The unique features and principles of taste-masking approaches used with ODT platforms are discussed, including the advantages and limitations of each technology. A brief discussion is also included on the taste masking of thin-film technologies, owing to their similar applications and requirements.This review elucidates the unique features of current commercially available or highly promising ODT and thin-film technologies, along with taste-masking approaches used in the manufacturing of oral solid dosage forms. A better understanding of these drug delivery approaches will help researchers to select the appropriate platform, or to develop innovative products with improved safety, compliance and clinical value.