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This study aims to model the prediction of two clinically relevant properties of drug delivery systems specifically for niosomes, i.e., particle size and drug entrapment efficiency (EE%) using a combined approach of data mining, artificial neural networks (ANN), and design of experiments (DoE). Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) system was adopted to screen published literature on niosomes that resulted in 17 articles with 114 formulations. Eleven properties (input parameters) related to drugs and niosomes affecting particle size and drug entrapment (EE%) (output variables) were precisely identified and used for the network training. The network architecture consists of 5 fully connected hidden layers with eleven hidden nodes in each layer, input layer has eleven nodes where each of these nodes maintains omnidirectional injective relation with the corresponding hidden node. The hyperbolic tangent sigmoid transfer function (HTSTF) with Levenberg-Marquardt backpropagation (LMB) was used to train the model. The network showed the highest prediction accuracy of 93.76% and 91.79% for EE% and particle size prediction. Sensitivity analysis identified drug/lipid ratio and Cholesterol/Surfactant ratio as the most significant factors affecting EE% and particle size of niosomes. Accordingly, nine Donepezil hydrochloride (DNPZ) noisome batches were prepared using a 3x3 factorial design with drug/lipid ratio and cholesterol/surfactant ratio as factors to validate the developed model for a new drug. The model was able to reach a prediction accuracy of more than 97% for experimental batches. Finally, the superiority of global ANN was demonstrated compared to the local RSM model for DNPZ niosome formulations. In conclusion, this study has demonstrated the use of the data mining approach to group published scattered information and formulate a data set to train the ANN that can help to design an optimum formulation and processing parameters for a clinically viable medicine with minimum time, cost, and efforts. However, the key challenge in forming an efficient ANN lies in having a suitable large data set and using the correct algorithm for the network.

Colorectal cancer is considered the third most frequent malignant neoplasm occurring in both men and women worldwide. Most approaches that have been used to fight and treat this type of malignancy are either invasive or nonselective. Noninvasive therapy using oral route can increase patient compliance and reduce treatment costs. Innovative measures such as use of nanotechnology and theranostic systems have been initiated in the oral therapy, which has been proven to be greatly advantageous in decreasing side effects, improving detection and diagnoses. This manuscript investigates recent innovative and novel therapeutic approaches through oral route and potential targets in the treatment of colorectal cancer.

Ocular drug delivery has remained as one of the most challenging task for pharmaceutical scientists. Compared with drug delivery to other parts of the body, ocular drug delivery has met with significant challenges posed by various ocular barriers. Effective treatment of ocular diseases especially in posterior ocular segments is a challenging task for formulation scientists because of the various barriers rendered by anatomy and physiology of the human eye. Much of the emphasis has been given to achieve noninvasive sustained drug release for eye disorders in both segments. Many polymeric systems utilizes viscosity modification, mucoadhesion, and in situ gelling for prolonging retention time, and reducing administration frequency have been developed for anterior drug delivery segment of the eye. On the other hand, biodegradable and nonbiodegradable polymeric implants for sustained drug delivery for chronic vitreoretinal diseases have been developed. Colloidal polymeric carriers are increasingly being studied for their applications. This chapter thoroughly discusses different drug delivery systems that utilizes polymers in ocular drug delivery.

Over the last decades, systemic drug delivery through oral mucosa has received a great deal of attention. Actually buccal mucosa is an attractive route due to its ease of accessibility, rapid efficacy, smooth and relatively immobile surface, high patient compliance, avoidance of gastrointestinal or hepatic first pass metabolism and suitability for the placement of controlled-release systems. However, the limitations in buccal drug delivery are related to the low permeability of the epithelium, relatively small surface area available for absorption and short residence time of formulations due to involuntary swallowing and constant salivary scavenging within the oral cavity. To provide a better retention of the dosage form in the site of application, bioadhesive polymers have been used extensively in buccal drug delivery systems. This chapter focuses on bioadhesive polymers used in buccal drug delivery. This chapter also provides insights into novel polymeric drug delivery systems such as hydrogels, microspheres, nanoparticles, patches, and matrix tablets used in buccal drug delivery.

BACKGROUND In order to prove the validity of a new formulation, a considerable amount of effort is required to study bioequivalence, which not only increases the burden of carrying out a number of bioequivalence studies but also eventually increases the cost of the optimization process. OBJECTIVE The aim of the present study was to develop sustained release matrix tablets containing diclofenac sodium using natural polymers and to demonstrate step by step process of product development till the prediction of in vivo marketed product equivalence of the developed product. METHOD Different batches of tablets were prepared by direct compression. In vitro drug release studies were performed as per USP. The drug release data were assessed using model-dependent, modelindependent and convolution approaches. RESULTS Drug release profiles showed that extended release action were in the following order: Gum Tragacanth > Sodium Alginate > Gum Acacia. Amongst the different batches prepared, only F1 and F8 passed the USP criteria of drug release. Developed formulas were found to fit Higuchi kinetics model with Fickian (case I) diffusion-mediated release mechanism. Model- independent kinetics confirmed that total of four batches were passed depending on the similarity factors based on the comparison with the marketed Diclofenac. The results of in vivo predictive convolution model indicated that predicted AUC, Cmax and Tmax values for batch F8 were similar to that of marketed product. CONCLUSION This study provides simple yet effective outline of pharmaceutical product development process that will minimize the formulation development trials and maximize the product success in bioequivalence studies.

Over the years, patient convenience and patient compliance-orientated research in the field of drug delivery has resulted in bringing out potential innovative drug delivery options. Out of which, medicated chewing gum (MCG) offers a highly convenient patient-compliant way of dosing medications, not only for special population groups with swallowing difficulties such as children and the elderly, but also for the general population, including the young generation.In this review, various formulation ingredients, different manufacturing processes, and assessment of in vivo and in vitro drug release from MCG are thoroughly discussed along with the therapeutic potential and limitations of MCG.Readers will gain knowledge about the rationale and prominent formulation and performance evaluation strategies behind chewing gum as a drug delivery system.The availability of directly compressible co-processed gum material enables rapid, safe and low-cost development of MCG as a drug delivery option. By MCG formulation, revitalization of old products and reformulation of new patented products is possible, to differentiate them from upcoming generics competition in the market.

The ultimate goal of any drug delivery system is the successful delivery of the drug to the body; however, patient compliance must not be overlooked. Fast dissolving drug delivery systems, such as, Mouth Dissolving Films (MDF), offer a convenient way of dosing medications, not only to special population groups with swallowing difficulties such as children and the elderly, but also to the general population. MDF are the novel dosage forms that disintegrate and dissolve within the oral cavity. Intra-oral absorption permits rapid onset of action and helps by-pass first-pass effects, thereby reducing the unit dose required to produce desired therapeutic effect. The present review provides an overview of various polymers that can be employed in the manufacture of MDF and highlights the effect of polymers and plasticizers on various physico-mechanical properties of MDF. It further gives a brief account of formulation of MDF and problems faced during its manufacture.

The therapeutic efficacy of anti-HIV agents is often hampered by poor bioavailability and lack of drug penetration in infected target tissues and cells. Using different types of nanotechnology-based delivery systems, it is possible to engineer strategies that can improve the therapeutic efficacy in HIV/AIDS by delivering drugs to cellular and anatomical viral reservoirs. The rationale for the use of nanocarrier systems relies on the fact that different types of therapeutic payloads can be encapsulated and the systemic pharmacokinetics and distribution are dictated by the properties of the nanocarriers rather than the drugs. The versatility of nanoplatforms can be further exploited in a formulation that has enhanced oral bioavailability, protects against degradation upon oral or systemic administration and prolongs the residence time at the target site. Nanocarriers can facilitate lymphatic transport, delivery across the blood–brain barrier, and efficient internalization in cells by nonspecific or receptor-mediated endocytosis. In this review, we will address the role of nanotechnology-based delivery systems in improving the delivery efficiency of anti-HIV drugs to cellular and anatomical sites of interest. Specific published examples will be highlighted with emphasis on the role of polymeric nanoparticle micelles, liposomes and nanoemulsions in improving delivery efficiency.

Over the past several years, immunization and treatment of infectious diseases has undergone a paradigm shift. Stemming from the vaccine research and development, not only a large number of disease-specific vaccines have been developed, but also enormous efforts have been made to improve the effectiveness of vaccines in order to provide optimal immunization. Introduction of nanotechnology and the development of nanocarrier-based vaccines have started to receive a lot of attention in order to provide effective immunization through better targeting and by triggering antibody response at the cellular level. Also, in the past several years, attention is placed on routes of vaccine administration in order to induce both mucosal and systemic immunity against the pathogen. Through judicious selection of the nanocarrier systems and the vaccine antigen, an optimal immunization and protection can be induced. This review article focuses on the patented applications of nanocarrier-based vaccine formulations and delivery. We have examined the United States patent literature to select inventions that specifically address this strategic approach for prevention of infectious diseases.

The developed liposomal DPI of LEU (LLEUn-DPI) demonstrated approximately 50% bioavailability compared with SC route. The studies justify the role of the pulmonary route as a promising alternative to the presently available SC route. The components of liposomal vesicles may be suitably changed to achieve higher bioavailability. Pulmonary delivery of LEU is expected to help in improving patient compliance, self-administration and avoiding the complications related to injection procedure. The developed LEU-DPI may be employed for both male and female contraception and treatment of prostate cancer in men and early puberty in children. In women it may be used for ovarian, endometrial, pancreas, and breast cancer; endometriosis; Uterine Leiomyoma; and anemia due to uterine fibroid tumors. However, the role of LEU-DPI in clinical practice can only be justified only after in vivo studies on 2 species of animals followed by extensive clinical trials.

Oral-controlled and modified-release drug delivery systems with zero-order sustained-release kinetics have been developed and proven suitable for meeting increasingly sophisticated therapeutic needs. Nevertheless, the impact of basic chronobiology concepts on the practice of medicine is still ongoing and to address chronotherapy needs, various types of pulsatile drug delivery systems have been innovated. The purpose of this review is to highlight these innovations in the field of chronotherapy.The present review discusses in depth on recent patents and developments related to pulsatile drug delivery systems with eroding, soluble or rupturable barrier coatings, and systems with capsular structures. Besides focusing on all recent innovations, the review addresses the novelty and feasibility of all upcoming technologies being exploited considering pulsatile drug delivery systems.There has been a growing interest in pulsatile delivery, which generally refers to the liberation of drugs following a programmable and well-defined lag phase from the time of administration. From 1981 until the present date, patent publications related to pulsatile drug delivery have shown more promising systems with numerous developments in arena of drug delivery. Future development of chronotherapeutic medications requires proper assessment and integration with other emerging disciplines such as hydrogel and transdermal delivery systems. The selection of the appropriate chronopharmaceutical technology should take into considerations with the ease of manufacturing and the cost-effectiveness.

Disease management of outdoor patients is mainly affected by patient compliance to the drug therapy, which in turn is governed by patient convenience. Failure to follow through with a treatment decision is one of the biggest causes of unsuccessful medical care. At present, different formulation options are available for various drugs, and hence, the decision is based on the most convenient dosage form for the patient, along with optimum therapeutic benefits.This paper reviews various available formulation approaches, in the hope of improving patient convenience, compliance and the overall outcome of oral drug therapy.While parenterals are valued for their speed and efficiency of delivery, these systems generally score low on patient satisfaction surveys. The oral route is the preferred route for drug delivery, although it renders multiple obstacles to formulate a patient-convenient platform, such as unfavorable taste and swallowing difficulties. Transdermal drug delivery also provides high patient satisfaction, but is effective only for the delivery of smaller, lipophilic molecules. The increasing development of biopharmaceutical therapies renders an increasing number of challenges for formulation scientists to develop a more patient-convenient means of drug delivery.

With the advancement of tablet manufacturing process, the demand of excipients with improved functionalities, mainly in terms of flow and compression properties, has increased. Coprocessed excipients are a mixture of two or more existing excipients at subparticle level, offer substantial benefits of the incorporated excipients and minimize their drawbacks. These multipurpose excipients have dramatically reduced the number of incorporating excipients in the tablet. The present review discusses the potential advantages of coprocessing and coprocessed excipients, material characteristics required for coprocessing, methods of coprocessing and various coprocessed excipients for direct compression available in the market.

The objective of this study was to develop and evaluate squalane oil-containing water-in-oil-in-water (W/O/W) multiple emulsion for mucosal administration of ovalbumin (OVA) as a model candidate vaccine in BALB/c mice. Control and optimized OVA-containing W/O/W emulsion (OVA-Emul) and chitosan-modified W/O/W emulsion (OVA-Emul-Chi) formulations were administered intranasally and orally at an OVA dose of 100 mug. The mucosal and systemic immune responses were evaluated after the first and second immunization. The OVA-Emul formulations resulted in higher immunoglobulin-G (IgG) and immunoglobulin-A (IgA) responses as compared with aqueous solution. In addition, significant IgG and IgA responses were observed after the second immunization dose using the emulsions with both routes of administration. Intranasal vaccination was more effective in generating the systemic OVA-specific IgG response than the mucosal OVA-specific IgA response. Oral immunizations, on the other hand, showed a much higher systemic IgG and mucosal IgA responses as compared with the nasally treated groups. The results of this study show that squalane oil-containing W/O/W multiple emulsion formulations can significantly enhance the local and systemic immune responses, especially after oral administration, and may be adopted as a better alternative in mucosal delivery of prophylactic and therapeutic vaccines.

Nanotechnology has shown tremendous promise in target-specific delivery of drugs and genes in the body. Although passive and active targeted-drug delivery has addressed a number of important issues, additional properties that can be included in nanocarrier systems to enhance the bioavailability of drugs at the disease site, and especially upon cellular internalization, are very important. A nanocarrier system incorporated with stimuli-responsive property (e.g., pH, temperature, or redox potential), for instance, would be amenable to address some of the systemic and intracellular delivery barriers. In this review, we discuss the role of stimuli-responsive nanocarrier systems for drug and gene delivery. The advancement in material science has led to design of a variety of materials, which are used for development of nanocarrier systems that can respond to biological stimuli. Temperature, pH, and hypoxia are examples of “triggers” at the diseased site that could be exploited with stimuli-responsive nanocarriers. With greater understanding of the difference between normal and pathological tissues and cells and parallel developments in material design, there is a highly promising role of stimuli-responsive nanocarriers for drug and gene delivery in the future.

Many drugs are not being effectively and efficiently delivered using conventional drug delivery approach to brain or central nervous system (CNS) due to its complexity. The brain and the central nervous system both have limited accessibility to blood compartment due to a number of barriers. Many advanced and effective approaches to brain delivery of drugs have emerged in recent years. Intranasal drug delivery is one of the focused delivery options for brain targeting, as the brain and nose compartments are connected to each other via the olfactory route and via peripheral circulation. Realization of nose to brain transport and the therapeutic viability of this route can be traced from the ancient times and has been investigated for rapid and effective transport in the last two decades. Various models have been designed and studied by scientists to establish the qualitative and quantitative transport through nasal mucosa to brain. The development of nasal drug products for brain targeting is still faced with enormous challenges. A better understanding in terms of properties of the drug candidate, nose to brain transport mechanism, and transport to and within the brain is of utmost importance. This review will discuss some pertinent issues to be considered and challenges to brain targeted intranasal drug delivery. A few marketed and investigational drug formulations will also be discussed.

Objective To ascertain the nasal bioavailability of Levonorgestrel and change formulation components to provide long-term effective concentrations of the drug in blood. An experimental study was conducted on rats to reduce dose and/or frequency of drug administration to reduce expected side effects reported in humans. Design In vivo study in rats. Setting Centre of Relevance & Excellence in new drug delivery systems, Pharmacy Dept., G.H. Patel Budg., Faculty of Technology and Engineering, M.S. University of Baruda, Fatehgunj, Vadodara, Gujarat, India. Animal(s) Rats of proven fertility. Intervention(s) Formulations containing 10-μg of levonorgestrel were administered in rats via the nasal route. Similarly, a 10-μg drug suspension was administered orally. The influence of the mucoadhesive agents chitosan and carbopol 934p on nasal absorption of the drug was also evaluated. Main outcome measure(s) Plasma drug concentration and pharmacokinetics. Result(s) Relative bioavailabilities of 29.93%, 32.14%, and 25.97% were observed after nasal administration of plain drug, physical mixture, and liposomal formulations, respectively. Mucoadhesive agents in nasal formulations were found to produce a threefold increase in drug bioavailability. Bioavailability was improved from 29.93% to 101.70% and 99.42%, respectively, for chitosan (0.5%) and carbopol 934p (0.5%) formulations, with a significantly improved plasma half life from 7.0 hours to 55.7 hours and 52.9 hours, respectively. Pharmacodynamic studies indicate that the dosing interval can be changed from daily oral administration to nasal administration once every 2 days without changing the dose. Conclusion(s) Levonorgestrel with mucoadhesive agents administered nasally in rats is superior for maintaining effective drug concentrations over an extended period of time when compared with the presently available orally administered form.

Introduction: 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. Anti-allergic, cetirizine (CTZ) is a BCS class-I (highly soluble and highly permeable) non-sedating antihistaminic drug and this study was based on the hypothesis that CTZ as a BCS class I drug 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. Materials and Methods: This study mainly focuses on taste masking of CTZ by inclusion complexation method, 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. A “chew out” study is carried out to assess in vivo drug release from MCG, in which residual amount is extracted from the chewed sample. Results: 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 flavors play a very essential character in its sensory properties. Conclusion: Interindividual 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.

The purpose of these studies was to achieve desired bioavailability after pulmonary administration of Levonorgestrel (LN) and to provide prolonged effective concentration of the drug in plasma and to reduce reported side effects of orally administered drug. The plain drug suspension, physical mixture (plain drug with liposomal constituents), and drug-encapsulated liposomes containing 10 micro g of drug were instilled intratracheally in rats. Similarly, 10- micro g drug suspension (LO) was administered orally. The blood samples were withdrawn at specific time intervals and were subjected to LN analysis by spectrofluorimetric technique. The plasma drug concentration data of both the treatments were plotted, and pharmacokinetics data were calculated and compared with that of oral administration. Percentage relative bioavailability (F*) of 97.6%, 98.6%, and 109.9% were observed after pulmonary administration of plain drug formulation (LP1), physical mixture (plain drug along with constituents of liposomes [LP2]), and liposomal (LP3) formulations of the drug, respectively. Following oral administration, Cmax of 14.4 +/- 0.6 ng/mL was observed at 2.1 +/- 0.2 hours followed by subtherapeutic concentration beyond 30 +/- 0.2 hours, while after pulmonary administration of LP1, LP2, and LP3 formulations, Cmax of 4.4 +/- 0.4 ng/mL, 4.2 +/- 0.5 ng/mL, and 4.4 +/- 0.6 ng/mL were observed at 6.0 +/- 0.2 hours, 7.0 +/- 0.2 hours, and 6.8 +/- 0.2 hours, respectively, followed by maintenance of effective plasma drug concentration up to 60 +/- 2 hours. These studies demonstrate superiority of pulmonary drug delivery with regards to maintenance of effective therapeutic concentration of the LN in the plasma over a period of 6 to 60 hours. Hence, the pulmonary delivery is expected to reduce frequency of dosing and systemic side effects associated with oral administration of LN.