Gingiva and anterior and posterior dorsum of tongue have significantly higher blood flows than all other regions; skin has a lower flow than the majority of oral regions; and palate has the lowest of all regions. In fact, the mean blood flow to the buccal mucosa in the rhesus monkey was observed to be 20.3 mL/min/100 g tissue as compared to 9.4 mL/min/100 g in the skin. Barriers to Permeation 5, 6, 7 : The main resistance to drug permeation is caused by the variant patterns of differentiation exhibited by the keratinized and non- keratinized epithelia. As mucosal cells leave the basal layer, they differentiate and become flattened. Accumulation of lipids and proteins also occurs. This further culminates in a portion of the lipid that concentrates into small organelles called membrane- coating granules (MCGs). In addition, the cornified cells also synthesize and retain a number of proteins such as profillagrin and involucrin, which contribute to the formation of a thick cell envelope. The MCGs then migrate further and fuse with the intercellular spaces to release the lipid lamellae.
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Distribution and retention time of the mucoadhesive tablets can be studied using the gamma scintigraphy technique. A study has reported the intensity and distribution of radioactivity in the genital tract after administration of technetium-labeled HYAFF tablets. Dimensions of the stomach part of the sheep can be outlined and imaged using labeled gellan gum, and the data collected are subsequently used to compare the distribution of radio labeled HYAFF formulations. The retention of mucoadhesive-radio labeled tablets based on HYAFF polymer was found to be more for the dry powder formulation than for the pessary formulation after 12 h of administration to stomach epithelium. The combination of the sheep model and the gamma scintigraphy method has been proved to be an extremely useful tool for evaluating the distribution, spreading, and clearance of administered stomach mucoadhesive tablets. Table 4 contains information about some commercially available mucoadhesive drug delivery systems.
Despite of tremendous advancement in drug delivery the oral route of drug administration is the most important method of administration of drug for systemic effect. The parenteral route is not routinely used for self administration of medication. It has been known for centuries that buccal and sublingual administration of drug solute is rapidly absorbed into the reticulated vein, which lies underneath the oral mucosa. The oral mucosa has rich blood supply and it is relatively permeable. The permeability of the buccal mucosa is 4- 1000 time greater then that of skin. the administration of drugs by the buccal route has several advantage over per oral administration such as QWICK ACTION, avoid of first pass metabolism , drug is not subject to acidic environment of the stomach and also the improved patient compliance particularly with pediatric & geriatric patient. It is the objective of this article to review the oral mucosal drug delivery by discussing briefly the structural feature of mucosa as drug delivery such as buccoadheshive film & tablet, medicated chew gum, fast dissolving tablet, film & capsule etc.
Oral mucosal drug delivery system is widely applicable as novel site for administration of drug and controlled release action by preventing first pass metabolism and enzymatic degradation due to GI microbial flora. The oral cavity represents a challenging area to develop an effective drug delivery modelling. This arises due to the various inherent functions of the oral cavity (eating, swallowing, speaking, chewing), as well as the presence of the fluid that is involved in all these activities, saliva. This fluid is continually secreted into and then removed from the mouth. Oral Mucosa drug delivery system provides local and systemic action. The delivery of drugs through the buccal mucosa has attracted much research interest over the past two decades and numerous approaches, both conventional and complex, have been developed in an attempt to deliver a variety of pharmaceutical compounds via the buccal route. To outline the progress in the in vitro and in vivo modeling of Mucosal drug delivery and provide a critical review of currently used methods. The purpose of this review is to represent the modeling of oral cavity with Mucoadhesive drug delivery systems and clarify the potential alternative to conventional therapy.
In recent years chewing gums are considered to be friendly oral mucosal drug delivery systems .5 Chewing gum has been used to deliver therapeutic agents such as nicotine for smoking cessation therapy (Batraet al., 2005; Moore et al., 2008).6 7 A medicated chewing gum is solid, single-dose preparation that is intended to be chewed for a certain period of time, deliver the drug and which may contain one or more than one active pharmaceutical ingredient (Mehta et al., 2010).8
Potential sites for Mucosal Drug Delivery: The primary objectives of mucoadhesive dosage forms are to provide intimate contact of the dosage form with the absorbing surface and to increase the residence time of the dosage form at the absorbing surface to prolong drug action 71 .The use of mucoadhesive formulations has been widely exploited for their targeted and controlled release delivery to many mucosal membrane-based organelles. Such formulations may deliver API for local or systemic effect, while bioavailability limiting effects such as enzymatic or hepatic degradation can be avoided or minimized 72 . The mucosa lines a number of regions of the body including the gastrointestinal tract, the urogenital tract, the airways, the ear, nose, and eye. These represent potential sites for attachment of any mucoadhesive system 71 .
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ABSTRACT: The study aims at development of patch from the herbal extracts (G.glabra & A.catechu), clove oil and other materials for oral mucosal drug delivery with more permeability and residence time. Materials and Methods: Oil i.e. clove oil, surfactant i.e. triethanolamine, co-surfactant i.e. propylene glycol was selected for the gel preparation. The gel was prepared using different combinations of surfactant, co-surfactant and polymer (HPMCK15M). Formulations were prepared in different batches (G1 to G4) and the prepared gel was evaluated in terms of physical appearance, acidity or basicity, nature with respect to viscosity, content of drug, spreadibility and release of drug in in- vitro condition. Results and Discussion: Upto 6 hours the maximum in vitro release was shown by formulations whereas after 6 hours the in vitro drug release was static. The batch G4 have proved to be a better formulation then other batches with respect to in-vitro the profile of release of drug as well as their viscosity. Conclusion: Utilization of cold method for preparing oral mucosal herbal gel of G.glabra & A.catechu extract has proved to be potent method. Thus in view of uncertainities regarding oral mucosal delivery of drug, the results looked quite promising.
Novel delivery of drugs via the gastrointestinal tract or airways is convenient for patients, although to date not efficient for non-permeating agents, notably protein based biologics or vaccines. The efficiency of mucosal delivery is compromised by potential degradation of proteins and peptides in the gastrointestinal tract, by the thickness of the mucus layer as well as by the low transport capacity of epithelial cells for uncleaved macromolecules. New treatments that enable tissue-specific delivery of bioactive agents would therefore offer significant benefits compared to systemic delivery. The aim of the present study was to develop a new delivery vehicle that would facilitate the rapid transportation of macromolecular agents upon mucosal administration.
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In order to prepare the target transdermal therapeutic system, 1% carbopol reservoir gel, polyethylene (PE), ethylene vinyl acetate copolymer (EVAC) membranes can be used as rate control membranes. If the drug is not soluble in water, propylene glycol is used for the preparation of gel. Drug is dissolved in propylene glycol; carbopol resin will be added to the above solution and neutralized by using 5% w/w sodium hydroxide solution. The drug (in gel form) is placed on a sheet of backing layer covering the specified area. A rate controlling membrane will be placed over the gel and the edges will be sealed by heat to obtain a leak proof device. 6. Aluminium backed adhesive film method: 58 Transdermal drug delivery system may produce unstable matrices if the loading dose is greater than 10 mg. Aluminium backed adhesive film method is a suitable one for preparation of same, chloroform is choice of solvent, because most of the drugs as well as adhesive are soluble in chloroform. The drug is dissolved in chloroform and adhesive
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4. Buffers: Nasal formulations are generally administered in small volumes ranging from 25 to 200 µL with 100 µL being the most common dose volume. Hence, nasal secretions may alter the pH of the administrated dose. This can affect the concentration of un-ionized drug available for absorption. Therefore, an adequate formulation buffer capacity may be required to maintain the pH in-situ. 5. Solubilizers: Aqueous solubility of drug is always a limitation for nasal drug delivery in solution. Conventional solvents or co-solvents such as glycols, small quantities of alcohol, Transcutol (diethylene glycol monoethyl ether), medium chain glycerides and Labrasol (saturated polyglycolyzed C8- C10 glyceride) can be used to enhance the solubility of drugs. Other options include the use of surfactants or cyclodextrins such as HP–ß-Cyclodextrin that serve as a biocompatible solubilizer and stabilizer in combination with lipophilic absorption enhancers. In such cases, their impact on nasal irritancy should be considered. 6. Preservatives: Most nasal formulations are aqueous based and need preservatives to prevent microbial growth. Parabens, benzalkonium chloride, phenyl ethyl alcohol, EDTA and benzoyl alcohol are some of the commonly used preservatives in nasal formulations. Mercury- containing preservatives have a fast and irreversible effect on ciliary movement and should not be used in nasal systems.
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as cross linker. The beads thus formed have been characterized by scanning electron micrographs (SEMs), electron dispersion X-ray analysis (EDAX), Fourier transform infrared spectroscopy (FTIR) analysis. The swelling of beads has been carried out as a function of various reaction parameters and pH of the swelling media. In addition, in vitro release dynamics of anti-ulcer model drug pantoprazole from drug loaded beads in different release media has been carried out for the evaluation of the drug release mechanism and diffusion coefficients. Release of drug from beads occurred through Fickian type diffusion mechanism.
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IT morphine trialing techniques are variable. Morphine trials have consisted of either bolus or continuous dose deliv- ered by an epidural or IT route. Some feel that continuous IT trials closely mimic the results of IDDS. There are advantages and disadvantages to each trialing method. The bolus mode of trialing drug delivery is less expensive requiring shorter hospital observation than continuous mode. The continuous mode increases the risk for infection and spinal cord damage. There is no evidence to support that one method is superior to another. The PACC guidelines strongly recommend at least 24-hour inpatient observation for trialing. 15
Recent studies indicate that sexual transmission of human immunodeficiency virus type 1 (HIV-1) generally results from productive infection by only one virus, a finding attributable to the mucosal barrier. Surprisingly, a recent study of injection drug users (IDUs) from St. Petersburg, Russia, also found most subjects to be acutely infected by a single virus. Here, we show by single-genome amplification and sequencing in a different IDU cohort that 60% of IDU subjects were infected by more than one virus, including one subject who was acutely infected by at least 16 viruses. Multivariant transmission was more common in IDUs than in hetero- sexuals (60% versus 19%; odds ratio, 6.14; 95% confidence interval [CI], 1.37 to 31.27; P ⴝ 0.008). These findings highlight the diversity in HIV-1 infection risks among different IDU cohorts and the challenges faced by vaccines in protecting against this mode of infection.
the novel drug delivery technology is applied in herbal medicine, it may help in increasing the efficacy and reducing the side effects of various herbal compounds and herbs. This is the basic idea behind incorporating novel method of drug delivery in herbal medicines. Thus it is important to integrate novel drug delivery system and Indian Ayurvedic medicines to combat more serious diseases. For a long time herbal medicines were not considered for development as novel formulations owing to lack of scientific justification and processing difficulties, such as standardization, extraction and identification of individual drug components in complex polyherbal systems 24 .
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Abstract: The blood–brain barrier (BBB) plays a fundamental role in protecting and maintaining the homeostasis of the brain. For this reason, drug delivery to the brain is much more difficult than that to other compartments of the body. In order to bypass or cross the BBB, many strategies have been developed: invasive techniques, such as temporary disrup- tion of the BBB or direct intraventricular and intracerebral administration of the drug, as well as noninvasive techniques. Preliminary results, reported in the large number of stud- ies on the potential strategies for brain delivery, are encouraging, but it is far too early to draw any conclusion about the actual use of these therapeutic approaches. Among the most recent, but still pioneering, approaches related to the nasal mucosa properties, the permea- bilization of the BBB via nasal mucosal engrafting can offer new potential opportunities. It should be emphasized that this surgical procedure is quite invasive, but the implication for patient outcome needs to be compared to the gold standard of direct intracranial injection, and evaluated whilst keeping in mind that central nervous system diseases and lysosomal storage diseases are chronic and severely debilitating and that up to now no therapy seems to be completely successful.
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form is the main reason that it could become a successful vaccine carrier in the near future. Furthermore, the much improved properties of modified CMs (eg, TCMs), such as increased mucoadhesivity, membrane permeability, stability, and controlled/extended release of the encapsulated vac- cine, show that they are a promising candidate for a potent vaccine carrier system. Further research and the ability to modify chitosan may improve structural and physicochemi- cal properties, increasing the potential of CM systems. New possibilities in the field of targeted vaccine delivery may be unlocked once various specific ligands (targeting moieties such as mannose and folate) that can be conjugated with chitosan derivatives have been designed and examined for specific interactions with preferred cell types. However, there are many challenges including low physical and mechani- cal stability, irregular particle size and distribution, and low target specificity that have hindered the efficacy, practical use, and commercialization of CMs. Thus, considering these factors, carefully designed and better functionalized CMs could be prepared for fruitful future application.
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A further possibility for the production of drug nanocrystals in solid matrices is high-pressure homogenization in hot melts. It offers advantages over production in aqueous solution and subsequent spray drying. The process is completely anhydrous, avoiding possible drug degradation or instabilities. The production can directly be performed by hot high pressure homogenization in melted material 39,40 . The homogenizers Micron Lab 40, batch and continuous, were equipped with temperature control jackets placed around the sample/product containers. Working temperatures up to 100°C (heated with water) or higher (heated with silicon oil) can be selected depending on the melting temperature of the used matrix material. For batch operation, solidification has to be averted between each homogenizing cycle. For homogenizers working in the continuous mode, the product containers must be also heated.
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Targeted drug delivery to specific sites is the significant problem which is being faced by the researchers. The development of new colloidal carrier called nanosponges has the potential to solve these problems. Nanosponge is a novel and emerging technology which offers controlled drug delivery for topical use. In this review article, application of nanosponges, its preparation methods and evaluation have been discussed. Nanosponges play a vital role in targeting drug delivery in a controlled manner. A wide variety of drugs can be loaded into nanosponge for targeting drug delivery. Both lipophilic as well as hydrophilic drugs can be loaded into nanosponges. Nanosponge drug delivery system has emerged as one of the most promising fields in life science.
The goal of delivery system is to get optimal therapeutic management. But, it still remains a challenge in the field of pharmaceuticals for delivery of ionic species and some non ionic. Several transdermal approaches have been used and recently there has been a great attention in using iontophoretic technique for the transdermal drug delivery of medications, both ionic and non ionic. This technique of facilitated movement of ions across a membrane under the influence of an externally applied electric potential difference is one of the most promising physical skin penetrations enhancing method. The payback of using iontophoretic technique includes improved systemic bioavailability ensuing from bypassing the first metabolism. Variables due to oral administration, such as pH, the presence of food or enzymes and transit times can all be eliminated. This article is an overview of the history of iontophoresis, mechanism, principles and factors influencing iontophoresis and its application for various dermatological conditions.
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Drug delivery to brain is still a challenging task due to the presence of the blood–brain barrier (BBB), a very restrictive barrier mainly composed of tightly sealed endothelial cells. The anatomy and physiology of BBB strictly regulates the brain access and clearance of endogenous and exogenous molecules from the systemic circulation. It is estimated that more than 98% of the new discovered central nervous system (CNS) potential drugs does not cross the BBB, failing to achieve therapeutic concentration within the brain parenchyma. Recent developments in the field of molecular biology enabled scientists to better understand the BBB and thus delivery of drugs to the brain, particularly under different pathological conditions. The aims of this Review are to outline current research in the field of brain barriers, the main advances made since 2000, the barriers to progress, and to recommend research priorities and the resources needed to advance the field. Applications of nanotechnology in drug transport, receptor-mediated targeting and transport, and finally cell-mediated drug transport will be discuss in the review. The challenge of delivering an effective dose of drug to the brain is formidable; solutions will likely involve multiple strategies that take into account the novel drug delivery systems as well as BBB biology. Keywords: Blood–brain barrier, Drug delivery, Nanoparticles, Liposomes.