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Nanocomposites are materials that integrate either a unit of nanoscale material or multi-units of nanoscale material into a matrix of a standard substance. The main purpose of the current study is to fabricate and evaluate nanocomposite transdermal films of Etoricoxib. The transdermal films of etoricoxib were developed with a mixture of polymers viz. Eudragit RL-100 and HPMC K4M, with or without different percentages of multi-walled carbon nanotubes (MWCNT, 1, 3, 5, and 10%, w/w of total polymer) using solvent casting method. Various parameters including FT-IR, DSC, drug content, folding endurance, moisture content, moisture uptake, water vapour permeability (WVP), and in-vitro drug release employing Franz diffusion cell were assessed for the prepared films. The absence of interaction between the drug and polymers was confirmed by FT-IR and DSC studies. The thickness of the resulted films was within the range of 0.33±2.76 µm to 0.43±2.76 µm. The weights of prepared films were between 85.1±1.3 mg to 85.15±0.8 mg. The drug content was measured to be between 4.486 and 5.993 mg. The folding endurance of the developed films ranged from 237.33±7.8 to 342±6.5. The moisture content (%) was between 5.91 ± 1.2% and 8.84 ± 4.0%, whereas the percent moisture uptake of prepared films was observed to be between 8.23 ± 2.1% and 12.38 ±3.6%. The WVP of films was found to be 97.08 ± 0.57 g/m2/day to 194.17 ± 0.81 g/m2/day. In-vitro release studies revealed that formulation F4 prepared with an equal amount (50:50) of Eudragit RL-100 and HPMC K4M, and 5% MWCNT shows the highest drug release after 24 hr of study.The above results imply that the nanocomposite films could be an effective tool for transdermal delivery of etoricoxib and could act as a better prospect in replacing the oral dosage form.

Among various death-causing diseases, the morbidity and mortality related to cancer are the highest, with millions of new malignancies added to the tally every year and predicted to increase at a higher rate by 2030. Lung cancer is continued to be the leading cause of cancer death worldwide, with a share of 11.6% of all cancers. Since the start of the millennium, there has been a continuous effort to provide the benefits of probiotics in the management and treatment of cancer, particularly lung cancer. Probiotics are defined as “live microorganisms which, when administered in adequate amounts, confer health benefits on the host”. These include specific strains of bacteria and fungi. Bacterial strains belonging to Lactobacillus and Bifidobacterium have demonstrated promising results in the prevention, attenuation, and treatment of the progression of lung cancer. The present chapter focuses on the types and aetiology of lung cancer and the role and mechanism of action of probiotics in providing immunity against lung cancer.

The goal of the present study was to develop inclusion complexes and polymers dispersions of ramipril prepared by physical mixing, kneading, co-evaporation, and solvent evaporation methods to enhance drug solubility and dissolution rate, and thereby to reduce drug dose and side effects using selected hydrophilic carriers such as β-CD, PVP-K25, PEG 4000, and HPMC K100M. The prepared formulations were characterized for solubility and in-vitro drug release studies. The systematic optimization of formulations was performed using I-Optimal experimental design by selecting factors such as type of carriers (X1), drug: carrier ratio (X2), and method of preparation (X3), and response variables including percent yield (Y1), solubility (Y2), Carr’s index (Y3) and drug release in 30 min (Y4). Mathematical modeling was carried out using a quadratic polynomial model. The inclusion complex formulation (F27) was selected as an optimized batch by numerical desirability function and graphical optimization with the help of design space. The inclusion complex prepared by the co-evaporation method showed maximum drug solubility and released in pH 6.8 phosphate buffer compared to pure and other formulations. The inclusion complex is a feasible approach to improve the solubility, dissolution rate, bioavailability, and minimization of drugs’ gastrointestinal toxicity upon oral administration of ramipril.

The concept of "one size fits all" followed by the conventional healthcare system has drawbacks in providing precise pharmacotherapy due to variation in the pharmacokinetics of different patients leading to serious consequences such as side effects. In this regard, digital-based three-dimensional printing (3DP), which refers to fabricating 3D printed pharmaceutical dosage forms with variable geometry in a layer-by-layer fashion, has become one of the most powerful and innovative tools in fabricating "personalized medicine" to cater to the need of therapeutic benefits for patients to the maximum extent. This is achieved due to the tremendous potential of 3DP in tailoring various drug delivery systems (DDS) in terms of size, shape, drug loading, and drug release. In addition, 3DP has a huge impact on special populations including pediatrics, geriatrics, and pregnant women with unique or frequently changing medical needs. The areas covered in the present article are as follows: (i) the difference between traditional and 3DP manufacturing tool, (ii) the basic processing steps involved in 3DP, (iii) common 3DP methods with their pros and cons, (iv) various DDS fabricated by 3DP till date with discussing few research studies in each class of DDS, (v) the drug loading principles into 3D printed dosage forms, and (vi) regulatory compliance.

The prime objective behind this investigation was to plan a Letrozole enclosed adhesive transdermal patch; since the transdermal route is an outright attractive option concerning its route, convenience and safety. Letrozole, a non-steroidal type II aromatase inhibitor, is reported for treating breast tumours and in postmenopausal women. In this study, few factors confined to formulation such as drug-in-adhesive, enhancers and amount of drug-loaded were investigated. The procedure used supposedly involves, the incarnation of the LET in phospholipids exploiting to a spray dryer. FTIR, X-RD, and DSC techniques which are used to evaluate entrapment efficiency were employed to LET spray-dried powder (LT-SDP). The molecule size, polydispersity file, and the EE were allegedly found to be 284.0 nm, 0.247 and 59.08%. On adding LT-SDP to a cream base with peppermint and olive oil as regular infiltration, the optimized formulation showed superior skin targeting in both in vitro and in vivo observations post-study.In vivo bioavailability studies showed just about four-fold increment in the plasma whereas the mean residence time and half-life were reasonably higher as compared to the LET cream in plain. The in vivo results observed remarkable patch concurrence with the plasma fixations anticipated from the in vitro infiltration. As an outpatient convenience, avoidance of gastrointestinal incompatibility provides suitability for self-administration for breast cancer prevention and treatment.

Traditionally, the skin is considered as a protective barrier which acts as a highly impermeable region of the human body. But in recent times, it is recognized as a specialized organ that aids in the delivery of a wide range of drug molecules into the skin (intradermal drug delivery) and across the skin into systemic circulation (transdermal drug delivery, TDD). The bioavailability of a drug administered transdermally can be improved by several penetration enhancement techniques, which are broadly classified into chemical and physical techniques. Application of mentioned techniques together with efforts of various scientific and innovative companies had made TDD a multibillion dollar market and an average of 2.6 new transdermal drugs are being approved each year. Out of various techniques, the thermal ablation techniques involving chemicals, heating elements, lasers, and radiofrequency (RF) are proved to be more effective in terms of delivering the drug across the skin by disrupting the stratum corneum (SC). The reason behind it is that the thermal ablation technique resulted in improved bioavailability, quick treatment and fast recovery of the SC, and more importantly it does not cause any damage to underlying dermis layer. This review article mainly discussed about various thermal ablation techniques with commercial products and patents in each classes, and their safety aspects. This review also briefly presented anatomy of the skin, penetration pathways across the skin, and different generations of TDD. Graphical abstract.

Polymers are used in drug delivery devices for drug encapsulation and release. Natural polymers often have advantages such as biocompatibility, biodegradability and biologically recognizable moieties which support cellular activities, compared to synthetic polymers. Chitosan, a naturally occurring polysaccharide obtained from chitin, has recently drawn attention because chitosan is non-toxic, biocompatible, biodegradable, stable and sterilizable. The additional qualities of chitosan are the release rate of drug, easy modification, cross-linking ability with other polymers, antimicrobial properties, gel forming ability, bioadhesion, immunostimulation, activation of macrophages and gas permeability. Here, I review applications of chitosan in drug delivery. The properties of chitin and chitosan, and the mechanisms of drug release are also presented.

Background: Quality by Design (QbD) is associated with a modern, systematic, scientific and novel approach which is concerned with pre-distinct objectives that not only focus on product, process understanding but also lead to process control. It predominantly signifies the design and product improvement and the manufacturing process in order to fulfill the predefined manufactured goods or final products quality characteristics. It is quite essential to identify the desired and required product performance report, such as Target Product Profile, typical Quality Target Product Profile (QTPP) and Critical Quality Attributes (CQA). Methods: This review highlighted the concepts of QbD design space, for critical material attributes (CMAs) as well as the critical process parameters that can totally affect the CQAs within which the process shall be unaffected thus, consistently manufacturing the required product. Risk assessment tools and design of experiments are its prime components. Results: This paper outlines the basic knowledge of QbD, the key elements; steps as well as various tools for QbD implementation in pharmaceutics field are presented briefly. In addition to this, quite a lot of applications of QbD in numerous pharmaceutical related unit operations are discussed and summarized. Conclusion: This article provides a complete data as well as the roadmap for universal implementation and application of QbD for pharmaceutical products.

Background: Application of thermoreversible gel can be a solution to the low residence time of the topical dosage forms such as normal gel, ointment and cream on the skin surface. Addition of another polymer and a nanocomposite can improve the poor mechanical strength and fast drug release of poloxamer 407 (POL 407) gel. Therefore, it is essential to add xanthan gum (XG) and graphene oxide (GO, thickness 1-2 nm, lateral dimension 1-5 µm) to POL 407 gel to enhance the mechanical strength and to sustain the drug release from the gel. Methods: Thermal gel of ondansetron hydrochloride (OSH) containing nanocomposite was prepared by adopting cold method. Interaction between drug and polymers was studied using FTIR method, morphological investigation was carried out by optical and scanning electron microscopy method, and rheological study was performed employing rotational rheometer equipped with a cone/plate shear apparatus, gelation temperature by glass bottle method and ex vivo permeation study was performed with cylindrical glass diffusion cell. Skin irritation potential was measured using rat as a model animal. Results: The FTIR spectrum of the selected gel showed that there is shifting of O-H stretching vibration of a hydroxyl group from 3408.72 to 3360.49 cm-1 and appearance of a new band at 1083.01 cm-1. The spectrum of the selected gel also showed the absence of characteristic peaks of GO at 1625.49 cm- 1. This result indicated that there may be an interaction between OSH and GO and hydrogen bonding between XG and POL 407. The gelation temperature was found to be decreased with the increase in GO content from 14.1±1.21°C 13±0.97°C. SEM micrograph demonstrated the uniform dispersion and intercalation of GO sheets in the gel. All the gel formulations showed a pseudo-plastic flow. Ex vivo permeation study (for 24 hr) exhibited highest (6991.425 µg) and lowest (2133.262 µg) amount of drug release, for OG1 and OG5, respectively. This is attributed to an increase in viscosity which led to a decrease in drug permeation across the abdominal skin of rats. The OG1 formulation (without GO) showed the highest flux of 76.66 µg/cm2/h, permeability coefficient (Kp) of 5.111× 10-3 cm/h and enhancement ratio of 3.277 compared to OG5 containing highest amount (9% w/w) of GO. The selected gel was found to be physically stable and there was minimum irritation score. Conclusion: All the above results indicated that thermal gel containing nanocomposite sustained the drug release and can be considered as an alternative to the orally administered tablet of OSH.

The key objective of the current research was to fabricate and optimize Capecitabine (Cap)-loaded [poly(lactic-co-glycolic acid)] PLGA-based nanoparticles (NPs) by enabling quality by design (QbD) approach for enhancing antitumor activity by promising delivery of the drug at the colonic site. The current research was based on fabricating PLGA-based nanoparticles along with Eudragit S100 as enteric polymer employing solvent shifting method followed by optimization using QbD approach. This approach was found to be useful for understanding the multiple factors and their interaction influencing the product by utilizing Design of Experiment (DOE). Box-Behnken design (BBD) was adopted to achieve the required critical quality attributes (CQAs), i.e., minimizing particle size, maximizing entrapment efficiency, and minimizing PDI value. The optimized nanoparticles were lyophilized and characterized by FT-IR, DSC, TEM, DLS, MTT assay using HT-29 cell lines, and in vivo pharmacokinetic studies. The optimized PLGA-based nanoparticles were found to possess average particle size, PDI, zeta potential, and entrapment efficiency of 195 nm, 0.214, -6.65 mV, and 65%, respectively. TEM analysis revealed the spherical nature of nanoparticles. The FT-IR and DSC studies revealed no interaction. The bioavailability of Cap-loaded nanoparticles was found to be two fold increased than the pure drug, and also, it exhibited significantly more cytotoxic to tumor cells as compared to pure drug as confirmed by MTT assay. The optimized PLGA-based nanoparticles found to possess enhanced bioavailability and significantly more cytotoxic potential as compared to pure drug.

The key objective of the current research was to fabricate and optimize Capecitabine loaded PLGA based nanoparticles (NPs) by enabling Quality by Design (QbD) approach for enhancing antitumor activity by promising delivery of the drug at the colonic site. The current research was based on fabricating PLGA based nanoparticles along with eudragit S100 as enteric polymer employing solvent shifting method followed by optimization using QbD approach. This approach was found to be useful for understanding the multiple factors and their interaction influencing the product by utilizing Design of Experiment (DOE). Box- Behken Design (BBD) was adopted to achieve the required critical quality attributes (CQAs) i.e. minimizing particle size, maximizing entrapment efficiency and minimizing PDI value. The optimized nanoparticles were lyophilized and characterized by FT-IR, DSC, TEM, DLS, MTT assay using HT-29 cell lines and in vivo pharmacokinetic studies. The optimized PLGA based nanoparticles were found to possess average particle size, PDI, zeta potential as well as entrapment efficiency of 195 nm, 0.214, -6.65 mV and 65% respectively. TEM analysis revealed the spherical nature of nanoparticles. The FT-IR and DSC studies revealed no interaction. The bioavailability of Capecitabine loaded nanoparticles was found to be two fold increased than the pure drug and also it exhibited significantly more cytotoxic to tumor cells as compared to pure drug as confirmed by MTT assay using HT 29 cell lines. The optimized PLGA based nanoparticles found to possess enhanced bioavailability and significantly more cytotoxic potential i.e. antitumor activity as compared to pure drug.

The materials accomplished with both biodegradable and renewable properties are called “green” materials. The biodegradable property can solve the problem related to environment such as pollution, whereas renewable property can be exploited for sustainability. Many synthetic polymers are being widely used in many industrial sectors for various purposes. However, many of them are nonbiodegradable in nature, which are impacting our environment. Therefore they are being replaced with biodegradable polymers. Among many natural and synthetic biodegradable polymers, poly(vinyl alcohol) (PVA) attracted huge attention because of its important desired qualities such as biodegradable, biocompatible, water solubility, nontoxic, and noncarcinogenic. In addition, it can exist in both crystalline and amorphous form. Due to earlier qualities, it can be used in the fabrication of different forms of green materials such as hydrogel, films, scaffold, membranes, fibers, particulate systems, and composites. In this chapter, various fabrication techniques of earlier forms of PVA and their characterization are described.

Dosage forms are defined as the systems comprised of one or more active ingredients in association with inert excipients (additives) that constitute the vehicle or formulation matrix. These additives are usually incorporated in the formulation to enhance physical appearance (aesthetic value), facilitate handling, improve stability and potentially influence the absorption and/or bioavailability of the active ingredients. In this context, pharmaceutical semisolid dosage forms including ointment, cream and gels contain one or more medicaments dissolved in or dispersed in a suitable base and appropriate excipients such as emulsifier, gelling agent, viscosity modifiers, antimicrobial agents, antioxidants and or stabilizing agents. These conventional forms of semisolids are meant for delivering drugs into skin and body cavities. But, the recent development in semisolid dosage forms is mainly oriented towards the systemic circulation and more particularly site-specific delivery of drug in an amount, which can elicit therapeutic action. Therefore, this chapter focuses on recent advances in semisolid dosage forms to enhance their aesthetic value and to increase the drug permeation across the skin without impacting their stability, including micro- and nanoemulsion (NE) systems, bioadhesive/mucoadhesive gel, in situ gels (e.g., thermal gel), in situ injectable gels, semisolid containing vesicular systems (e.g., liposomes, ethosomes, niosomes, proniosomes, ethosomesand transfersomes, and 126particulate systems (such as polymeric micro- and nanoparticles, lipid-based particles), cryogels, and pluronic lecithin organogels (PLO). This article also discusses the theory of semisolids, new tools available for the evaluation of semisolids. Furthermore, regulatory requirements for the semisolid dosage forms are also described in this chapter.

The main objective of the present investigation was to develop transdermal films of ondansetron HCl (OS) with polyvinyl alcohol (PVA) using Box-Behnken design and to optimize them employing Derringer’s optimization tool. Design-Expert software was used to investigate the effect of independent variables such as concentration (%, w/w) of glycerol and 1,8-cineole, and number of Freeze-Thaw cycle (F-T cycle) on the dependent variables viz. ultimate tensile strength (UTS) and flux. The F-T cycle followed by solvent casting method was employed to develop films. Universal tensile testing machine and Franz diffusion cell were used to measure tensile strength and flux, respectively. Quadratic model was found to be best fit model and the effect of concentration of glycerol and the number of F-T cycle significantly influences the tensile strength (p

The transdermal drug-in-adhesive (DIA) patch of simvastatin (SM) was developed using acrylic adhesives such as DURO-TAK® 87-9301, DURO-TAK® 87-4287, DURO-TAK® 87-235A. The patches were evaluated for in vitro drug permeation across the pork ear skin using diffusion cell and stability studies. Among the three acrylic adhesives used, DURO-TAK® 87-9301 exhibited maximum flux (5.18 ± 0.23 µg/cm2/h). To further enhance the drug permeation, isopropyl myristate (IPM), d -limonene and 1,8-cineol as penetration enhancers (PEs) were incorporated into the DIA patch prepared from DURO-TAK® 87-9301. Out of those, IPM containing patch exhibited a flux of 16.45 ± 1.67 µg/cm2/h revealing that IPM is the best PE. The stability study was carried out on optimized fresh (SA4) and 6 months old patches stored at room and at accelerated condition (40 ± 2 °C/75 ± 5%RH) using FTIR, DSC and SEM techniques. Significant shift of peaks were not observed in FTIR spectra and DSC thermograms of the patches after the stability period. SEM micrographs of patches did not show any evidence of recrystallization indicating the presence of drug in the molecular form throughout the adhesive matrix. The investigation reveals that the DIA patch studied as above is stable and may serve as a potential drug delivery system for simvastatin.

Hydrogels are promising biomaterials because of their important qualities such as biocompatibility, biodegradability, hydrophilicity and non-toxicity. These qualities make hydrogels suitable for application in medical and pharmaceutical field. Recently, a tremendous growth of hydrogel application is seen, especially as gel and patch form, in transdermal drug delivery. This review mainly focuses on the types of hydrogels based on cross-linking and; secondly to describe the possible synthesis methods to design hydrogels for different pharmaceutical applications. The synthesis and chemistry of these hydrogels are discussed using specific pharmaceutical examples. The structure and water content in a typical hydrogel have also been discussed.

The present investigation is focused on the development of transdermal film-forming gel (FFG) loaded with etoricoxib employing research surface methodology (RSM). Box-Behnken surface design method was used to develop experimental run using different concentrations of etoricoxib, hydroxypropyl methylcellulose (HPMC K100M), and eudragit RL100 as independent variables, and Derringer's optimization tool was employed to optimize best possible formulation. The dependent variables considered in this study were viscosity and drug permeation at 24 h (Q24, μg/cm2). Anti-inflammatory study was performed on Wistar albino rats for 8 h. Skin irritation studies and accelerated stability studies were performed for validated FFG formulations. Quadratic model was found to be best fit model (p < 0.0001) for both the responses. The influence of HPMC concentration on the viscosity was found to be highest whereas concentration of etoricoxib was maximum for Q24. The optimum composition of the FFG was observed to be 4% of etoricoxib, 1.1246% of HPMC, and 0.4% of eudragit. Above composition resulted in viscosity of 1549.5 mPa.s and maximum Q24 of 4639.11 μg/cm2 with desirability 0.918. The in vivo anti-inflammatory study demonstrated better sustained release effect (for 8 h) of optimized FFG compared to orally administered drug suspension. An average irritation score of 0.555 was observed on Draize scoring system. The validated FFG formulation was found to be stable for the 3 months in accelerated conditions. It can be concluded from the above investigations that the validated FFG formulation of etoricoxib is well tolerated and could provide sustained drug release for 8 h. Graphical abstract.

Even though the concept of three-dimensional printing (3DP) technology was evolved in 1970s, but its popularity in pharmaceutical field grows manifold during last decade due to the introduction of the first Food and Drug Administration (FDA) approved 3D printed drug product (Spritam®) into the market. Since then, there has been an immense focus on 3DP research not only in the biomedical field but also in pharmaceutical sector. This is due to potential advantages possessed by 3DP techniques including the customization of medicines with an adjusted dose for individuals, on-demand manufacturing, and the ability to fabricate complex geometries and sophisticated dosage forms, and cost-effectiveness. In this review, the concept and process of 3DP, different methods and techniques of 3DP, excipients, and drug characteristics requirement, quality defects, product quality characterization, and current trends of 3D regulation. It also focussed on the application of 3DP in pharmaceutical dosage form development.

The aim of the present investigation was to prepare and optimize suitable combination of polymers hydroxypropyl methylcellulose (HPMC) and pluronic ® F127 (PN F127) for the development of thermosensitive gel of Metoprolol succinate (MS) using central composite design (CCD). The effect of formulation factors (concentration of HPMC and PN F127) on responses such as cumulative percentage release (CPR) of MS, bioadhesive force (BF) and viscosity was measured statistically. Quadratic model was found to be best fit model among different models used in the study. The optimum conditions were found to be 0.92% of HPMC and 15% of PN F127. Under these conditions, the predicted CPR, BF and viscosity were found to be 84.94 μg/cm 2 , 41.56 gf and 48.94 Pa s, respectively. Ex vivo permeation of MS from optimized thermosensitive gel across abdominal skin of rat demonstrated highest flux (64.35 μg/cm 2 /h) for the gel formulation containing 1,8-cineole (5% w/w). The hypotensive activity was performed on normotensive rabbits and the results showed that the optimized formulation prolonged the activity up to 12 h. The above findings indicated that thermosensitive gel of MS for skin application exhibited strong potential against hypertension and expected to provide a better alternative to oral MS formulations.

Polymers are major components of drug delivery systems in terms of drug encapsulation and release. Natural polymers offer advantages such as biocompatibility, biodegradability and biologically-recognizable moieties, which support cellular activities, compared to synthetic polymers. Chitosan, a naturally-occurring polysaccharide obtained from chitin, has drawn much attention in the pharmaceutical field because chitosan possess valuable properties such as non-toxic, biocompatibile, biodegradable, stable and sterilizable. The additional qualities of chitosan such as controlling the release rate of drug, scope for modification, cross-linking ability with other polymers, antimicrobial properties, gel forming ability, bioadhesion, immunostimulation, activation of macrophages, and gas permeability, make chitosan one of the most versatile co-polymer for drug delivery. This chapter discusses applications of chitosan in drug delivery, along with drug delivery systems that can be developed based on chitosan. Furthermore, the properties of chitin and chitosan and the mechanisms of drug release from chitosan-based drug delivery systems are presented.

In the present study, pluronic lecithin organogel (PLO) of diltiazem hydrochloride (DZH) was developed by taking different ratios of organic phase to aqueous phase (1:3, 1:4, and 1:5) with varying concentration of soya lecithin (20, 30, and 40 % w/w) in organic phase (isopropyl myristate, IPM) and pluronic (20, 25, and 30 % w/w) in aqueous phase, respectively, and characterized for in vitro parameters and ex vivo permeation study. The results of in vitro parameters were found to be within permissible limit and all the PLOs were physically stable at refrigeration and ambient temperature. The influence of phase ratio and different concentrations of soya lecithin on DZH release from the PLOs was found to be significant (p

The aim of this present study is to develop micro-beads for controlled release of Metoprolol succinate (MS). Different combinations of alginate and poloxamer 407 (PL) were taken to prepare beads by employing ionotropic gelation method, where CaCl2 used as gelling agent. FTIR technique was used to study the drug and polymers interaction. The prepared beads were evaluated for drug loading, entrapment efficiency, particle size and morphology, in vitro drug release and drug release kinetics. There were no shift in the major peaks of the pure drug was observed from the FTIR spectra, which indicates the absence of interaction between drug and polymers. The highest drug loading and entrapment efficiency were found to be 3.11 % and 35.67 %, respectively for the formulation FB1. The particle size was measured by sieving method and it was found that the particles were in the micron range for all the formulations. The morphology of the formulation FB4 was studied by SEM and the image showed irregular surface. The in vitro drug release study was carried out in pH 6.8 phosphate buffer for 12 hr at 37ºC and the results demonstrate cumulative percentage of drug release was decreased with the increase in PL ratio in the composition that indicates controlled drug release. To know the mechanism of drug release the in vitro drug release data were fitted to zero order, first order, Higuchi and Korsmeyer-Peppas equation. The formulation FB4 showed highest correlation coefficient (r2) of 0.97 for Higuchi equation due to which it was selected as best formulation. The release exponent (n) of all the formulation were below 0.45 except FB4 (0.48) demonstrating Fickian diffusion is the drug release mechanism, whereas the formulation FB4 indicated non-Fickian diffusion i.e. diffusion and erosion were the mechanism

Nanocomposites, nanosized particles in polymer/metal/ceramic matrix, are one of the highly talked technological products on 21st century, which have lived up to the expectation. These are having high potential in almost all industrial sectors owing to their improved properties in terms of mechanical, thermal, optical, electrochemical, biodegradable, biocompatible, etc. In recent years, it has been widely used in delivery of drug through various routes. Transdermal route, where the drug molecules have to penetrate through the skin and reach to systemic circulation, is one of such routes in which nanocomposites have tremendous application potential. This chapter has focused mainly on the types of nanocomposites and their application in transdermal drug delivery (TDD) in the form of hydrogel, membranes and films, pressure-sensitive adhesives (PSA), and microneedles with examples. It also discussed the fundamentals of TDD.

The aim of the present research was to optimize cryogel formulation of Diltiazem hydrochloride (DZ) with poly(vinyl alcohol) (PVA) and hydroxypropyl methylcellulose (HPMC) by utilizing response surface methodology followed by ex vivo permeation study on the optimized gel containing penetration enhancers. A 3-level factorial design was employed to formulate the experimental runs and to evaluate the effect of two independent variables such as the concentration of PVA and HPMC on characteristics of cryogel such as bioadhesive strength (BS) and in vitro drug release (dependent variables). Response surface plots such as contour and 3D plots were generated by the Design Expert® software to analyze the effect of independent variables on dependent variables. Fourier transform infrared spectroscopy studies confirmed the absence of interaction between DZ and polymers. Among various models generated by the software, quadratic model was found to be best fit for both the responses. Both the formulation factors influenced BS synergistically. However, the effect of HPMC concentration was more pronounced compared to concentration of PVA. But, an opposite effect shown by both the formulation factors on cumulative percentage of drug release (CPR) in 8 h. The optimized batch of cryogel of DZ selected by the software was having composition of 5 % of PVA and 2 % of HPMC. Penetration enhancers such as 1,8-cineole, d-limonene and carvone were incorporated into the optimized gel and permeation study was carried out using abdominal skin of rat. The study demonstrated a highest flux of 118 ± 5.81 µg/cm2/h in case of 1,8-cineole containing gel followed by carvone and d-limonene.

The objective of the present investigation is to develop topical gel of minoxidil using model polymers such as hydroxypropyl methylcellulose K4M (HPMC K4M) and hydroxypropyl cellulose (HPC) at different concentrations (1, 2 and 3%) individually and in combination. The dmg and polymers compatibility study was carried out by FTIR teclmique. The gels were evaluated for dmg content, viscosity, pH, homogenity, grittiness and in vitro dmg release. The FTIR spectra of dmg alone and in physical mixture with polymers did not show any slıift in majör peaks, wlıich indicates no dmg-polymer interaction. Ali the data obtained from above physicochemical parameters were satisfactory. In vitro dmg release of gels was performed using Franz diffusion celi of 25 ınL capacity with cellulose acetate membrane in phosphate buffer pH 6.8 as receptor medium. According to the release study, the dmg release was decreasing with the increasing polymer concentration in each fonnulation. The correlation coefficient (r) values demonstrate that the dmg release pattem followed Higuclıi model and the release exponent (n) values were witlıin 0.45 to 0.85 for ali fonnulations except FG3, FG4 and FG7. The above results showed that swelling and diffusion (Non-Fickian diffusion) were the dmg release mechanism. To know the marketing feasibility, the release data of ali the fonnulations were compared with the marketed formulation (Tugain gel) and it was found tlıat formulation FG2 was lıaving lıighest similarity with similarity factor (f2) of 77.79

In the current study Indomethacin (IM) fast dissolving tablets (FDTs) were prepared by direct compression technique in order to enhance its dissolution rate. The tablets were formulated using two different approaches; super-disintegration and efferves-cence. A combination formulation of above approaches was also developed to further improve its properties. The super-disintegrants used in the formulae were sodium starch glycolate (Primogel), cross-povidone (Kollidon) and cross-carmellose (Ac-di-sol). Sodium bicarbonate and citric acid combination was employed as effervescent ingredients. The prepared powder mixtures of IM were subjected to evaluation of various pre-compression parameters and tablets were evaluated for weight variation, dimension, hardness, friability, drug content, disintegration, wetting time, uniformity of dispersion, in vitro drug release and stability studies. The FT-IR spectra shown there are no interaction between of IM with excipient. The results of pre-compression studies indicate acceptable flow property for all the powder mixtures. The data of weight variation, dimension, hardness, friability, uniformity of dispersion and drug content studies were within the official limits. The wetting time and disintegration time decreases considerably with the increase in super-disintegrants amount. By using the combination approach, the disintegration and wetting time further decreased. In vitro dissolution studies were carried out using phosphate buffer pH 6.8 as dissolution medium for 60min and observed that formulation IF9, among super-disintegration approach, released highest percentage (97.13±2.09) of IM. In vitro drug release was highest (98.54±2.89) at 60 min for formulation IF11, when all the formulations were taken into consideration. The stability study was performed on the promised formulation IF11 at 40±2 o C/ 75±5% RH for 3 months and the results indicated that there were no significant changes in aforesaid tablet properties.

The purpose of the present study was to develop a bilayer tablet of zolpidem tartrate (ZT) using sodium starch glycolate (SSG) as superdisintegrant in the immediate release (IR) layer and hydrophilic polymers such as hydroxypropyl methylcellulose (HPMC K4M), metalose 90 SH 4000, carbapol 974 PNF in sustained release (SR) layer. Both the IR and SR granules of ZT were evaluated for bulk density, tapped density, angle of repose, Carr’s index, Hausner ratio and loss on drying. All the values were found to be satisfactoy. The prepared bilayer tablets were evaluated for weight variation, hardness, friability, drug content, in vitro drug release, FT-IR studies, similarity factor and stability studies. In vitro dissolution studies were carried out in a USP dissolution apparatus I using 500mL of 0.01N HCl as dissolution medium. The formulations gave an initial burst effect to provide the loading dose of the drug followed by sustained release for 4 h. The data obtained were fitted to Zero order, First order, Higuchi’s model and Korsmeyer-Peppas equations. The release exponent (n) values for all the formulations were less than 0.45 indicating Fickian diffusion was the drug release mechanism. FT-IR studies indicated that there are no drug-excipient interactions. The similarity factor (f2) was calculated by comparing dissolution data of all the formulations with that of marketed bilayer tablet of ZT (Ambien CR). The f2 value was highest (70) for the formulation SF8 and was selected as promising formulation among all the developed formulations. The stability study was performed on the formulation SF8 at 25oC/60% RH, 30oC/75% RH and 40oC/75% RH (accelerated condition) for 3 months. The results indicated that there were no significant changes in aforesaid tablet properties.

The purpose of the research work was to develop a floating drug delivery System of ritonavir (RN) in order to prolong the gastric resideııce time and im rense its bioa\’ailability. The floating tablets of RN were prepared bv direct compression techniqııe, using polymers such as different grades of hydroxypropvl methyfçellulose (HPMÇ, Methocel E15LV, E50LV, K100LV and K4M) and poly\’invl pvrrolidone (PVP K30). Sodiıım bicarbonate w as used as gas releasing agent. The formıdations w ere optimized on the basis of matris integritv, duration offloating, swelling behavior and in vitro drug release. Escept series FA, w here floating time was 10 hr, other series such as FB, FC and FD w ere showing more than 12 hr offloating time. The highest average swelling index of 170.68 ± 0.45 was found in FD3 batch. The in vitro drug release indicated estended release of RN and more than 62 percent of drug was released at the end of the 12 hr for ali the batches, The mechanism of RN release from the floating tablets for FA, FB and FC series is anomaloııs diffusion transport andfollows zero order kinetics, but FD series indicated Higuchi kinetics with release rate esponent (n) of 0.44. Further, the scanning electron microscopy showed porous structured formed on the tablet surface at different times (0, 3, 6, 9 and 12 hr) of dissolution for the selected batch FC3. Finallv, FC3 batch showed no signifıcant change in above parameters after storage atroom temperature (28-32°C% 40°C and 50°Cfor one month

The use of topical formulation is popular over the past decade due to extensive researches made in the field of transdermal drug delivery. As a result, an increasing number of drugs are being added to the list of therapeutic agents that can be delivered to systemic circulation through the skin. Commonly available dosage forms for the topical application are creams, ointments, gels, patches etc. The therapeutic benefits of the above topical formulations are limited due to barrier property of stratum corneum (SC). The use of chemical penetration enhancers (CPEs) is one of the long standing approach to overcome the barrier property of SC. Numerous class of novel compounds have been evaluated for penetration enhancement activity, including soft enhancement for percutaneous absorption (SEPA), for example, 2 N-nonyl-1,3- dioxolanes, N-acetyle prolinate esters (such as pentyl- and octyl-N-acetyle prolinate), alkyldiloxanes (e.g., 1-Alkyl-3-b-D glucopyranosyl-1,1,3,3-tetramethyl disiloxanes), transcarbam (such as 5-(dodecyloxycarbonyl) pentylammonium-5- (dodecyloxycarbonyl) pentylcarbamate), iminosulfurane (like N-hexyl,N-benzoyl-S,S-dimethylimino-sulfuranes), capsaicin derivatives (e.g., Nonivamide), cinnamene compounds (such as cinnamic acid, cinnamaldehyde etc), terpenes (like clove and basil oil) and synergestic combination of penetration enhancers (SCOPE). We briefly describe about the anatomy of skin. Potential mechanisms of action of above novel PEs along with adverse reactions associated with traditional PEs are also considered in this review.

The present investigation focused on the development of Diltiazem HCl (DTH) matrix film and its characterization by in-vitro, ex-vivo and in-vivo methods. Films were prepared by solvent casting method by taking different ratios of hydroxypropyl methylcellulose K4M (HPMC K4M) and Eudragit RS100. Various parameters of the films were analyzed such as mechanical property using tensile tester, interaction study by Fourier transform infrared spectroscopy (FTIR) and Thermogravimetric analysis (TGA), in-vitro drug release through cellulose acetate membrane, ex-vivo permeation study using abdominal skin of rat employing Franz diffusion cell, and in-vivo antihypertensive activity using rabbit model. The FTIR studies confirmed the absence of interaction between DTH and selected polymers. Thermal analysis showed the shifting of endothermic peak of DTH in film, indicating the dispersion of DTH in molecular form throughout the film. Incorporation of 1,8-cineole showed highest flux (89.7 μg/cm(2)/h) of DTH compared to other penetration enhancers such as capsaicin, dimethyl sulfoxide (DMSO), and N-methyl pyrrolidone (NMP). Photomicrographs of histology study on optimized formulation (DF9) illustrated disruption of stratum corneum (SC) supporting the ex-vivo results. The in-vivo antihypertensive activity results demonstrated that formulation DF9 was effective in reducing arterial blood pressure in normotensive rabbits. SEM analysis of films kept for stability study (40 ± 2 °C/75% ± 5%RH for 3 months) revealed the formation of drug crystals which may be due to higher temperature. The findings of the study provide a better alternative dosage form of DTH for the effective treatment of hypertension with enhanced patient compliance.

Matrix type of simvastatin transdermal film (SSTF) was developed with poly(vinyl alcohol) (PVA) and eudragit RL100 (EG) using response surface methodology (RSM) to investigate combined effect of the selected process variables like SS concentration, PVA:EG ratio and the dibutyl phthalate (DBT) concentration at different levels on dependent variables such as tensile strength and flux, with an aim to optimize a suitable combination of drug, polymer and plasticizer ratio. The study reveals that the effect of DBT concentration was highest on tensile strength, while SS concentration exhibited pronounced effect on SS flux through the abdominal skin of rat. According to Derringer's desirability prediction tool, the composition of optimized film was found to be 2% of SS, 2:1 ratio of PVA:EG and 40% of DBT. Under these conditions, the SSTF exhibited a predicted value of tensile strength and flux of 11.871 MPa and 43.569 μg/cm(2)/h, respectively. The in vivo hypolipidemic study conducted for 14 days in hyperlipidemia induced Sprague-Dawley rats reveals that the optimized SSTF exhibited significant lowering of blood lipid level. The absence of skin irritation indicates that the prepared film was safe and well tolerated as transdermal formulation. Thus, the film may serve as an alternative therapy to oral dosage form of SS.

Since the approval of first transdermal patch (Transderm Scop(®)) containing scopolamine in 1979, the improvement in systemic drug delivery through skin remains incremental. The traditional methods based on passive diffusion of drug molecules in to the skin are unable to deliver macromolecules, such as peptides, proteins, DNA and vaccines, due to the barrier properties of stratum corneum (SC). During the course of approximately 35 years, the focuses are not only to overcome the above barrier property of the skin but also the safety, accuracy and patient compliance aspect of the traditional methods. The former limitation can be overcome by altering the SC barrier function by different active methods such electrically assisted methods (sonophoresis, iontophoresis, electroporation, magnetophoresis, pressure waves, electron beam irradiation), SC abruption (microneedles, high-velocity jet) and SC removal (tape-stripping, suction, microdermabrasion, ablation). This review summarizes basic principles, mechanisms, advantages, limitations and recent development of above physical techniques along with skin anatomy and drug transport pathways across skin.

In the present scenario, most of the developed and new discovered drugs are posing real challenge to the formulation scientists due to their poor aqueous solubility which in turn is responsible for poor bioavailability. One of the approach to overcome above problem is the packaging of the drug in to particulate carrier system. Among various carriers, lipid emerged as very attractive candidate because of its unique property of enhancing the bioavailability of poorly water soluble drugs. Solid lipid, one of the physical forms of lipid, is used to formulate nanoparticles, popularly known as Solid lipid nanoparticles (SLNs), as an alternative carrier system to emulsions, liposomes and polymeric micro- and nano-particles. SLNs combine advantages of the traditional systems but avoid some of their major disadvantages. This paper reviews numerous production techniques for SLNs along with their advantages and disadvantages. Special attention is paid to the characterization of the SLNs by using various analytical tools. It also emphasizes on physical state of lipid (supercooled melts, different lipid modifications).