Fast dissolving films: a review

Fast-dissolving drug delivery systems have been developed as an alternative to conventional dosage form as an oral means of drug delivery in case of chronic conditions. Now a day's fast dissolving films are preferred over conventional tablets and capsules for masking the taste of bitter drugs to increase the patient compliance. Fast dissolving films consist of a very thin oral strip which dissolves in less than one minute when placed on the tongue. Dissolvable oral thin films are in the market since past few years in the form of breath strips and are widely accepted by consumers for delivering vitamins, vaccines and other drug products. The various manufacturing techniques for the preparation of films have also been detailed in the review. The present review details most of the patents on such fast dissolving films in recent years. A brief study has been made on various parameters which are used to evaluate such films. In case of chronic disorders these fast dissolving films are better for delivering drugs and obtaining faster therapeutic blood levels and superior in comparison to other oral conventional dosage forms.     

In vitro and in vivo characterization of domperidone-loaded fast dissolving buccal films

The delivery of drugs via fast dissolving films is an effective alternative for drugs with low bioavailability when administered by other routes. This is the case of domperidone (DMP) an anti-emetic drug with low water solubility and vulnerable to extensive first-pass effect. To overcome these limitations, in this work, we designed and produced fast dissolving muco-adhesive buccal films of domperidone using varying amount polyvinylpyrrolidone (PVP K-90) using the solvent casting method. Films loaded with more than 10% of drug were not homogenous and opaque as indicated by white patches of drug in the film matrix. Formulation of DMP in the film form resulted in conversion of the drug from crystalline state to the semi-crystalline state as indicated by X-ray powder diffraction analysis. Moreover, about 40% of drug loaded within the films was released during the first five minutes compared to only about only 6.5% of pure drug in drug dissolution assays in vitro. In vivo pharmacokinetics analysis revealed that the DMP-loaded film had higher maximum plasma concentration (C_max) and shorter time to reach C_max (T_max) than a commercially available tablet formulation. In conclusion, the produced DMP buccal film formulation showed high absorption rate, rapid onset of action, and improved bioavailability compared with the conventional tablet. Our findings may support the development of novel dosage forms for the transmucosal delivery of DMP for convenient, rapid, and effective treatment of nausea and vomiting.     

Drug nanosuspensions: a ZIP tool between traditional and innovative pharmaceutical formulations

Introduction: A nanosuspension or nanocrystal suspension is a versatile formulation combining conventional and innovative features. It comprises 100% pure drug nanoparticles with sizes in the nano-scale range, generally stabilized by surfactants or polymers. Nanosuspensions are usually obtained in liquid media with bottom-up and top-down methods or by their combination. They have been designed to enhance the solubility, the dissolution rate and the bioavailability of drugs via various administration routes. Due to their small sizes, nanosuspensions can be also considered a drug delivery nanotechnology for the preparation of nanomedicine products.

Areas covered: This review focuses on the state of the art of the nanocrystal-based formulation. It describes theory characteristics, design parameters, preparation methods, stability issues, as well as specific in vivo applications. Innovative strategies proposed to obtain nanomedicine formulation using nanocrystals are also reported.

Expert opinion: Many drug nanodelivery systems have been developed to increase the bioavailability of drugs and to decrease adverse side effects, but few can be industrially manufactured. Nanocrystals can close this gap by combining traditional and innovative drug formulations. Indeed, they can be used in many pharmaceutical dosage forms as such, or developed as new nano-scaled products. Engineered surface nanocrystals have recently been proposed as a dual strategy for stability enhancement and targeting delivery of nanocrystals.     

Exploring novel approaches to vaginal drug delivery

Vaginal route serves as a potential site of drug administration for local and systemic absorption of a variety of therapeutic agents. Despite being a non- invasive route of drug administration, the vagina has not been extensively explored as compared to other routes. Intravaginal drug delivery has been traditionally restricted to delivery of antinfectives to the local vaginal cavity. Concerted efforts have been made in the recent past to rediscover the vaginal route as a potential route for the delivery of therapeutically important molecules, proteins, peptides, small interfering RNAs, oligonucleotides, antigens, vaccines and hormones. The understanding of vaginal physiology has led to the design of specific intravaginal drug delivery systems to reach the systemic circulation. To overcome the limitations of conventional dosage forms administered through vaginal route various novel approaches like the use of mucoadhesive or bioadhesive polymers, pH- or temperature-sensitive polymers, liposomes, nanoemulsions, nanoparticles, vaginal inserts, multiple emulsions and hydrogels have been designed which enable controlled and prolonged release of drugs. The present article is a comprehensive review of the research and patents encompassing conventional dosage forms used for vaginal drug delivery with emphasis on newer platform technologies pertaining to intravaginal administration.     

Bacteria and pH-sensitive polysaccharide-polymer films for colon targeted delivery

The colon provides drug delivery opportunities for colon-specific and systemic delivery of various therapeutic agents. Different strategies have been utilized in targeting drugs to the colon. Recently, integrated systems which incorporate dual mechanisms in colon targeted delivery have received a lot of attention. Of particular interest is bacteria-aided biomaterials and pH-sensitive polymeric film (BPSF) coating for colon targeted drug delivery. The major constituents of these films are polysaccharides and pH-sensitive polymers. The pH-sensitive polymer retards drug release in the stomach and small intestine, while the polysaccharide is digested by colonic enzymes. Digestion of the polysaccharides by bacterial glycosidic enzymes increases the pore density in the film to facilitate drug release. Generally, bacteria-aided biomaterials and pH-sensitive films can be applied to the delivery of most small organic molecules to the colon. The review encompasses the pharmaceutical design parameters such as film digestibility, swelling index and dry mass loss (that provide molecular mechanistic analysis of film permeability) as well as tensile strength, elastic modulus, and elongation at break (that describe the desirable mechanical properties of the films). A critical analysis of formulation, techniques for characterization of film properties and drug-release kinetics from these systems are emphasized.     

Exploring the use of novel drug delivery systems for antiretroviral drugs

Novel drug delivery systems present an opportunity for formulation scientists to overcome the many challenges associated with antiretroviral (ARV) drug therapy, thereby improving the management of patients with HIV/AIDS. This paper provides a comprehensive review of the various ARV delivery systems that have been developed for achieving sustained drug release kinetics, specifically targeting drugs to the macrophages, brain and gastric mucosa, and for addressing formulation difficulties such as poor solubility, stability and drug entrapment. Studies on the potential of systems for alternative routes of ARV drug administration, i.e., transdermal, buccal and rectal, are also highlighted. The physico-chemical properties and the in vitro/in vivo performances of various systems such as sustained release tablets, ceramic implants, nanoparticles, nanocontainers, liposomes, emulsomes, aspasomes, microemulsions, nanopowders and Pheroid^TM are summarised. Further studies that remain to be undertaken for formulation optimisation are also identified. This review highlights the significant potential that novel drug delivery systems have for the future effective treatment of HIV/AIDS patients on ARV drug therapy.     

Chitosan-polycarbophil complexes in swellable matrix systems for controlled drug release

A prerequisite for progress in the design of novel drug delivery systems is the development of excipients that are capable of fulfilling multifunctional roles such as controlling the release of the drug according to the therapeutic needs. Although several polymers have been utilised in the development of specialised drug delivery systems, their scope in dosage form design can be enlarged through combining different polymers. When a polymer is cross-linked or complexed with an oppositely charged polyelectrolyte, a three-dimensional network is formed in which the drug can be incorporated to control its release. The swelling properties and release kinetics of two model drugs with different water solubilities (i.e. diltiazem and ibuprofen) from monolithic matrix tablets consisting of an interpolyelectrolyte complex between chitosan and polycarbophil are reported. Matrix tablets consisting of this polymeric complex without drug or excipients exhibited extremely high swelling properties that are completely reversible upon drying. The drug release from matrix systems with different formulations depended on the concentration of the chitosan-polycarbophil interpolyelectrolyte complex and approached zero order release kinetics for both model drugs. The chitosan-polycarbophil interpolyelectrolyte complex has demonstrated a high potential as an excipient for the production of swellable matrix systems with controlled drug release properties.     

Current knowledge on biodegradable microspheres in drug delivery

Introduction: Biodegradable microspheres have gained popularity for delivering a wide variety of molecules via various routes. These types of products have been prepared using various natural and synthetic biodegradable polymers through suitable techniques for desired delivery of various challenging molecules. Selection of biodegradable polymers and technique play a key role in desired drug delivery.

Areas covered: This review describes an overview of the fundamental knowledge and status of biodegradable microspheres in effective delivery of various molecules via desired routes with consideration of outlines of various compendial and non-compendial biodegradable polymers, formulation techniques and release mechanism of microspheres, patents and commercial biodegradable microspheres.

Expert opinion: There are various advantages of using biodegradable polymers including promise of development with different types of molecules. Biocompatibility, low dosage and reduced side effects are some reasons why usage biodegradable microspheres have gained in popularity. Selection of biodegradable polymers and formulation techniques to create microspheres is the biggest challenge in research. In the near future, biodegradable microspheres will become the eco-friendly product for drug delivery of various genes, hormones, proteins and peptides at specific site of body for desired periods of time.     

Vaginal Films for Drug Delivery

Vaginal dosage forms have been studied in relation to many drugs as the vagina presents several advantages as a site for drug delivery, such as large surface area, rich blood supply, avoidance of the first-pass effect, relatively high permeability to several drugs, and self-insertion. Traditional vaginal dosage forms have been associated with disadvantages such as low residence time and discomfort and have been surpassed by newly designed drug delivery systems, particularly those based on bioadhesive polymers. Vaginal films are solid dosage forms that rapidly dissolve in contact with vaginal fluids and are unlikely to be associated with leakage and messiness. They have been studied for some female genital problems, aiming either contraceptive, antimicrobial, or microbicide effects. Precise and complex processes of manufacturing and characterization are required to achieve successful film formulation. Although scarce, the available user's acceptability studies show promising results. Vaginal films gather a lack of opportunities for both therapeutic and prophylactic actions, and therefore should be considered when designing and developing new vaginal drug delivery systems. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:2069–2081, 2013     

Nanomedicine and experimental tuberculosis: facts, flaws, and future

Nanoparticle-based drug delivery systems form the crux of nanomedicine and are suitable for targeting chronic diseases such as tuberculosis. Extensive experimental data supports the possibility of intermittent chemotherapy with key first-line as well as second-line antituberculosis drugs by employing synthetic or natural carriers, chiefly polymers. Besides sustained release of drugs in plasma and organs, other potential advantages of the system include the possibility of selecting various routes of chemotherapy; reduction in drug dosage, adverse effects, and drug interactions; and targeting drug-resistant and latent bacteria. On the other hand, the choice of carrier, large-scale production, stability, and toxicity of the formulation are some of the major issues that merit immediate attention and resolution. Nevertheless, keeping in view the hurdles in new antituberculosis drug development, nanomedicine has provided a sound platform and a ray of hope for an onslaught against tuberculosis. FROM THE CLINICAL EDITOR: Tuberculosis remains a major public health concern worldwide. In this paper, the role and significance of nanoparticle-based drug delivery systems are discussed for targeting tuberculosis, including strains that are drug resistant with conventional methods.     

Mucoadhesive microspheres: a promising tool in drug delivery

Mucoadhesive polymers have recently gained interest among pharmaceutical scientists as a means of improving drug delivery by promoting the residence time and contact time of the dosage form with the mucous membranes. Mucoadhesion is the process whereby synthetic and natural polymers adhere to mucosal surfaces in the body. If these materials are then incorporated into pharmaceutical formulations, drug absorption by mucosal cells may be enhanced or the drug will be released at the site for an extended period of time. Microspheres, in general, have the potential to be used for targeted and controlled release drug delivery; however, coupling of mucoadhesive properties to microspheres has additional advantages like, a much more intimate contact with the mucus layer, efficient absorption and enhanced bioavailability of the drugs due to a high surface to volume ratio. The present review describes the potential applications of mucoadhesive microspheres as a novel carrier system to improve drug delivery by various routes of administration like buccal, oral, nasal, ocular, vaginal and rectal, either for systemic or for local effects. The mucoadhesive polymers, methods of preparation of microspheres and their in vitro and in vivo evaluation are also described.     

High-throughput screening of PLGA thin films utilizing hydrophobic fluorescent dyes for hydrophobic drug compounds

Hydrophobic, antirestenotic drugs such as paclitaxel (PCTX) and rapamycin are often incorporated into thin film coatings for local delivery using implantable medical devices and polymers such as drug-eluting stents and balloons. Selecting the optimum coating formulation through screening the release profile of these drugs in thin films is time consuming and labor intensive. We describe here a high-throughput assay utilizing three model hydrophobic fluorescent compounds: fluorescein diacetate (FDAc), coumarin-6, and rhodamine 6G that were incorporated into poly(d,l-lactide-co-glycolide) (PLGA) and PLGA–polyethylene glycol films. Raman microscopy determined the hydrophobic fluorescent dye distribution within the PLGA thin films in comparison with that of PCTX. Their subsequent release was screened in a high-throughput assay and directly compared with HPLC quantification of PCTX release. It was observed that PCTX controlled-release kinetics could be mimicked by a hydrophobic dye that had similar octanol–water partition coefficient values and homogeneous dissolution in a PLGA matrix as the drug. In particular, FDAc was found to be the optimal hydrophobic dye at modeling the burst release as well as the total amount of PCTX released over a period of 30 days. © 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:4317–4329, 2011     

The effect of pectin on swelling and permeability characteristics of free films containing Eudragit RL and/or RS as a coating formulation aimed for colonic drug delivery

BACKGROUND AND THE PURPOSE OF THE STUDY: The potential of pectin as a bacterially degradable polysaccharide for colon drug delivery has been demonstrated. Due to the high solubility and swelling properties of pectin in aqueous media, it is frequently used in combination with water insoluble polymers for targeting drugs to the colon. The aim of this study was to evaluate free films containing pectin as a bacterially-degradable polysaccharide in combination with Eudragit RL (ERL) and/or RS (ERS) as a coating formulation for colonic drug delivery. METHODS: Isolated free films comprising 20% pectin and 80% ERL or ERS and their combination in 1:1 ratio were prepared by casting method. Then, free films were evaluated by water vapor transmission (WVT), swelling and permeability experiments for theophylline and indomethacin in different media. RESULTS: Formulations containing ERL exhibited higher WVT, swelling and permeability compared with formulations containing ERS. The permeability of theophylline through free films composed of pectin and eudragit polymers in simulated colonic media was not significantly different from those obtained in other media. However indomethacin free films containing pectin and ERL showed higher permeation in simulated colonic fluid (SCF) compared to the other media. MAJOR CONCLUSION: Formulation containing pectin and ERL may be suitable as a coating formulation for colon targeted delivery of drugs of low solubility such as indomethacin.     

Cyclodextrin-based controlled drug release system

Because of their bioadaptability and multi-functional characteristics, cyclodextrins (CDs) are capable of alleviating the undesirable properties of drug molecules in various routes of administration through the formation of inclusion complexes. This article outlines the current application of natural and chemically modified CDs in the design of advanced dosage forms. In an oral drug delivery system (DDS), the hydrophilic and ionizable CDs can serve as potent drug carriers in the immediate release- and delayed release-formulations, respectively, while the release rate of water-soluble drugs can be retarded by hydrophobic CDs. Since CDs are able to extend the function of pharmaceutical additives, the combination of molecular encapsulation with other carrier materials will become effective and a valuable tool in the improvement of drug formulation. Moreover, the most desirable attribute for the drug carrier is its ability to deliver a drug to a targeted site; conjugates of a drug with CDs can be a versatile means of constructing a new class of colon-targeting prodrugs. On the basis of this knowledge, the advantages and limitations of CDs in DDS are addressed.     

Oral delivery of HIV-protease inhibitors

Strategies for optimizing the oral delivery of HIV-protease inhibitors draw from drug discovery efforts in molecular design, drug development tools in dosage formulation, and dosage regimen considerations in clinical medicine. This review outlines the evolution of these strategies for drugs that have been approved for human use, drug candidates still in development, and molecules that are no longer in development but from which valuable delivery information was obtained. Molecular design for obtaining desirable pharmacokinetics following oral administration primarily involved maximizing aqueous solubility and minimizing first-pass metabolism. Optimization of molecular design for oral drug delivery purposes is tempered by additional considerations for drug potency, toxicity, potential for interactions, and development of viral resistance. Strategies for improving oral bioavailability through dosage formulation use information from the effects of coadministered meals on drug plasma levels. Patient adherence to dosage regimens remains a major issue in assuring effective oral drug treatment and in preventing the development of resistance. Progress has been made in clinical studies where improved oral bioavailability and reductions in drug plasma level variability have been achieved with appropriate dosage regimen adjustment.     

Preparation of a novel floating ring capsule-type dosage form for stomach specific delivery

Study objectives were to develop a unique floating ring capsule dosage form which combines gastric soluble and insoluble portions, and to evaluate its suitability for stomach specific drug delivery. New floating ring capsules were developed using different polymers and were compared for various parameters. The formulation with HPMC and sodium CMC has better floating properties. The effects of polymers concentration on drug release were studies by in vitro release studies. The interaction studies of combined drug with polymers were determined using FT-IR spectroscopy. The entrapped air within the gel barrier and lower densities of HPMC and sodium CMC resulted in better floating behavior. Steady slow gel formations showed prolonged drug release. The in vitro release rates were generally found to be faster with low concentration of carbopol showing release within 2 h, while formulations containing high amount of HPMC showed release in 8 h. In particular, the higher concentration of HPMC formulation shows the best drug release performance. A very low change in peak shift was observed only with sodium alginate formulations. Further, FT-IR measurements confirmed the absence of any chemical interactions. Results indicate that new floating ring capsule is a promise dosage form for stomach specific delivery.     

Drug release kinetics and physicochemical characteristics of floating drug delivery systems

INTRODUCTION: Absorption of drugs through the gastrointestinal tract poses a variety of limitations, making the in vivo performance of drug delivery systems uncertain. Following on from recent advances, in a time of increased consideration of floating drug delivery systems, it is as important as ever to continue the progress by studying different aspects of these systems. Moreover, it seems imperative to gain a deeper insight into drug release mechanisms, in order to design a more systematic and intellectual floating system. AREAS COVERED: This paper summarizes current approaches in the research and development of ideal floating drug delivery systems, from recent literature. Also, in order to have predictability and reproducibility in designing an efficient floating dosage form, some kinetic studies are mentioned, and the drug release mechanism from floating drug delivery systems is discussed. EXPERT OPINION: Developing an efficient floating dosage form is reliant on a better understanding of the relation between formulation variables and performance of the floating systems. Generally, the combination of two buoyancy mechanisms and gas-generating systems with swellable polymers would be beneficial for obtaining an appropriate floating lag time and duration of buoyancy, which in turn guarantees optimum efficiency of the pharmaceutical dosage form.     

Delivery of bioactive peptides and proteins across oral (buccal) mucosa

The identification of an increasing array of highly potent, endogenous peptide and protein factors termed cytokines, that can be efficiently synthesized using recombinant DNA technology, offers exciting new approaches for drug therapy. However, the physico-chemical and biological properties of these agents impose limitations in formulation and development of optimum drug delivery systems as well as on the routes of delivery. Oral mucosa, including the lining of the cheek (buccal mucosa), floor of mouth and underside of tongue (sublingual mucosa) and gingival mucosa, has received much attention in the last decade because it offers excellent accessibility, is not easily traumatized and avoids degradation of proteins and peptides that occurs as a result of oral administration, gastrointestinal absorption and first-pass hepatic metabolism. Peptide absorption occurs across oral mucosa by passive diffusion and it is unlikely that there is a carrier-mediated transport mechanism. The principal pathway is probably via the intercellular route where the major permeability barrier is represented by organized array of neutral lipids in the superficial layers of the epithelium. The relative role of aqueous as opposed to the lipid pathway in drug transport is still under investigation; penetration is not necessarily enhanced by simply increasing lipophilicity, for other effects, such as charge and molecular size, also play an important role in absorption of peptide and protein drugs. Depending on the pharmacodynamics of the peptides, various oral mucosal delivery systems can be designed. Delivery of peptide/protein drugs by conventional means such as solutions has some limitations. The possibility of excluding a major part of drug from absorption by involuntary swallowing and the continuous dilution due to salivary flow limits a controlled release. However these limitations can be overcome by adhesive dosage forms such as gels, films, tablets, and patches. They can localize the formulation and improve the contact with the mucosal surface to improve absorption of peptides and proteins. Addition of absorption promoters/permeabilizers in bioadhesive dosage forms will be essential for a successful peptide/protein delivery system.     

Diverse approaches for the enhancement of oral drug bioavailability

In conscious and co-operating patients, oral drug delivery remains the preferable route of drug administration. However, not all drugs possess the desirable physicochemical and pharmacokinetic properties which favor oral administration mainly due to poor bioavailability. This has in some cases led to the choice of other routes of administration, which may compromise the convenience and increase the risk of non-compliance. Poor bioavailability has necessitated the administration of higher than normally required oral doses which often leads to economic wastages, risk of toxicity, erratic and unpredictable responses. The challenge over the years has been to design techniques that will allow oral administration of most drugs, irrespective of their properties, to achieve a therapeutic systemic availability. This will be a worthy achievement since over 90% of therapeutic compounds are known to possess oral bioavailability limitations. In this review, an attempt has been made to explore various approaches that have been used in recent years to improve oral drug bioavailability, including physical and chemical means. This review strives to provide a comprehensive overview of advances made over the past 10 years (2000-2010) in the improvement of the oral bioavailability of drugs. Briefly, the design of prodrugs to bypass metabolism or to enhance solubility as well as modification of formulation techniques such as the use of additives, permeation enhancers, solubilizers, emulsifiers and non-aqueous vehicles have been discussed. Arising approaches, such as formulation modification techniques; novel drug delivery systems, which exploit the gastrointestinal regionality of drugs, and include the pharmaceutical application of nanotechnology as an emerging area in drug delivery; inhibition of efflux pumps; and inhibition of presystemic metabolism have been more extensively addressed. This critical review sought to assess each method aimed at enhancing the oral bioavailability of drugs in terms of the purpose, scientific basis, limitations, commercial application, as well as the areas in which current research efforts are being focused and should be focused in the future.