The Plasma Membrane

The plasma membrane retains the contents of the cell and acts as a permeability barrier. That is, it allows only certain substances to enter or leave the cell, and the rate of entry is strictly controlled. Early researchers recognised that hydrophobic materials entered cells easily and proposed that an oily or 'lipoidal' layer was present at the cell surface. Gorter and Grendel in 1925 estimated the thickness of this layer by extracting the oily membrane from erythrocytes with acetone and...

Patterns Of Motility In The Small Intestine

The small intestine, like the stomach, displays two distinct patterns of motility. The fed pattern is characterized by random motor activity, in groups of 1 to 3 sequential contractions, separated by 5 to 40 seconds of inactivity. The physical and chemical nature Figure 6.5 Segmental contractions (left) and propulsive contractions (right) of the small Figure 6.5 Segmental contractions (left) and propulsive contractions (right) of the small of the food determines the number of contractions for...

The cornea

The cornea is made up of the stroma (up to 90 of its thickness) which is bounded externally by epithelium and the Bowman's membrane and internally by Descemet's membrane and the endothelium (Figure 11.2). The mean thickness of the cornea in man is just over 0.5 mm in the central region and is composed of five to six layers of cells. It becomes 50 thicker towards the periphery as the epithelium increases to eight to ten cell layers. The cells at the base are columnar, but as they are squeezed...

Anatomy And Physiology

The nose is a prominent structure located on the face between the eyes. The external openings are known as nares or nostrils which open at the back into the nasopharynx and lead to the trachea and oesophagus. The nose is the primary entrance to the respiratory tract, allowing air to enter the body for respiration. It conditions inspired air by filtering, warming, and moistening it. The nose also contains the olfactory organ, essential for the sense of smell. The nasal cavity is an...

Intercellular Routes Of Absorption

As well as being absorbed through the epithelial cells, molecules can pass through tissues via the intercellular or paracellular route through junctional gaps between cells. There has been much discussion regarding the importance of this process in transport across the gastrointestinal mucosa. There is considerable variation in the integrity of the tight junctions along the gastrointestinal tract, with the membranes of the stomach and large intestine having the highest transepithelial...

Small intestinal transit time of dosage forms

During fasting, both monolithic and multiparticulate dosage forms will be swept rapidly through the small bowel by the migrating myoelectric complex. The action is propulsive and not mixing in nature, thus a capsule containing pellets given on an empty stomach may leave the stomach and pass down the small intestine as a bolus with minimal dispersal27. The increased dispersal of pelleted formulations within the small intestine when the formulations are taken with a meal occurs because the...

Drug Distribution Following Parenteral Administration

The blood transports the drug to the tissues, however the drug concentration in the tissues is usually not equal to that in the blood. A number of factors influence the drug concentration in tissues, one of the most important being the blood flow per unit mass of the tissue. Tissues can be broadly classified as poorly-perfused, adequately perfused and well-perfused on this basis as shown in Table 2.1. Note how organs with a relatively small mass, such as the heart and brain, only require a...

Introduction

The term parenteral drug delivery covers a number of administration routes, which have little in common other than the fact that they generally involve the use of a hypodermic needle to inject the drug into the body. This route bypasses a number of physiological barriers and hence the constraints on the composition and formulation of the medicine are much more rigorous than for less invasive routes such as oral or transdermal delivery. Despite this a surprising range of materials can be...

Transport Across Cell Membranes

In order to function correctly a cell must be able to take up and release a wide range of materials for drug therapy to be successful it must also be possible to get therapeutic substances into cells and across layers of cells such as epithelia. There are a number of possible mechanisms for transport across membranes substances may simply diffuse across, or be carried by a range of more selective processes, depending on the substance involved. Studies using model membranes have revealed that...

Vehicles And Devices

Transdermal Drug Delivery Device

For topical delivery of drugs, ointments, creams, lotions and gels are used. These materials have a long history but are not suitable for controlled transdermal delivery since they do not provide a protected reservoir of drug or a controlled area of application. There are at least four systems currently employed for systemic delivery of drugs (Figure 8.3). All of these have two main features a reservoir containing the drug, and a physical mechanism to control the rate at which drug diffuses...

Bacterially triggered systems

Sulphasalazine (salicylazosulphapyridine) was one of the earliest prodrugs used in the treatment of inflammatory bowel disease. It contains 5-aminosalicyclic acid (mesalazine) linked covalently to sulphapyridine. 5-aminosalicyclic acid (5-ASA) is not effective orally because it is poorly absorbed, and is inactivated before reaching the lower intestine therefore prior to its administration as a prodrug, its was only effective when given as a suppository or a rectal suspension enema. The prodrug...

Organisation of the stomach

Gastric Parietal Cell Distribution

The stomach can also be divided into three anatomical regions (Figure 5.1). The uppermost part is the fundus, which after a meal is often seen to contain gas. It also produces slow sustained contractions which exert a steady pressure on the gastric contents gradually pressing them in an aboral direction. The largest part of the stomach is the body which acts as a reservoir for ingested food and liquids. The antrum is the lowest part of the stomach. It is almost funnel-shaped, with its wide end...

Gastric Emptying Of Dosage Forms

For the majority of cases, oral drug delivery is the cheapest and most convenient method of dosing. Unfortunately it is difficult to achieve a precise control of the plasma concentration-time profile, which shows marked intra- and inter-subject variation even under the rigidly controlled conditions of the clinical trial. In the unrestricted patient this is exaggerated by poor compliance and anything more complicated than a b.d. schedule is impractical. Daily patterns such as food intake,...

T

T cells Lymphoid cells from the bone marrow that migrate to the thymus gland, where they develop into mature differentiated lymphocytes that migrate between the blood and lymph. Mature T cells are antigen specific i.e. each responds to different antigens. Tachycardia Abnormal rapid heartbeat. Talin A sweet-tasting protein extracted from Thaumatococcus danielli, approximately 100,000 times sweeter than sucrose. Also known as Thaumatin. Technetium-99m (99mTc) A gamma emitting radioisotope with a...

Epithelium

The nasal cavity, the nasopharynx, larynx, trachea and bronchi are lined with pseudostratified, ciliated, columnar epithelium with many goblet cells. There are also coarse hairs in the nasal region of the respiratory tract. The bronchi, but not the bronchioles, have mucous and serous glands present. The bronchioles, however, possess goblet cells and the wall contains a well-developed layer of smooth muscle cells, capable of narrowing the airway. The epithelium in the terminal and respiratory...

D

Danazol Drug which inhibits pituitary gonadotrophins. Decongestant sprays Nasal aerosols which unblock the congested nasal airways. Decylmethyl sulphoxide A powerful hydrophobic solvent used as a transdermal penetration enhancer. Defaecation The expulsion of faeces. Deltoid muscle Triangular muscle which covers the shoulder. Deoxycorticosterone A hormone from the adrenal gland which controls salt and water metabolism. Dermis The inner layer of the skin, lying beneath the epidermis. Descemet's...

Menopause

The menopause is associated with a gradual change in the vagina which can take up to 5 to 8 years to stabilise. The length and the diameter decrease with age and the pH can rise to between 6 and 8 increasing the risk of infection. Elasticity and blood supply decrease with age and the upper vagina may atrophy. The epithelium becomes thinner which is an important consideration in intravaginal drug delivery since this would lead to an increased permeability. Vaginal secretions and hence...

Structure Of The Skin

The skin is elastic and quite rugged despite the fact that it is only approximately 3 mm thick. It consists of three anatomical layers, the epidermis, the dermis and a subcutaneous fat layer (Figure 8.1). The epidermis is a thin, dry and tough outer protective outer layer. It forms a barrier to water, electrolyte and nutrient loss from the body, and at the same time is also responsible for limiting the penetration of water and foreign substances from the environment into the body. Damage or...

Dispersion Of Dosage Forms In The Stomach

Of in vitro dissolution tests however this is often not the case. Endoscopy has demonstrated that when multiple tablets are administered, all lie in the same place in the stomach, at the base of the greater curvature. This is a particular problem with formulations which cause gastric irritation or damage, for example non-steroidal anti-inflammatory drugs which can produce focal erosions due to repeated insult to a small area of the mucosa. Iatrogenically-produced ulcers can often be...

Secretion and absorption of water

An adult human takes in roughly 1 to 2 litres of dietary fluid every day. In addition, another 6 to 7 litres of fluid is received by the small intestine as secretions from salivary glands, stomach, pancreas, liver and the small intestine itself. By the time the ingesta enters the large intestine, approximately 80 of this fluid has been absorbed. The absorption of water is absolutely dependent on absorption of solutes, particularly sodium. Within the intestine, there is a proximal to distal...

Nasal Drug Delivery References 2016

Nasal Allergy. 2nd edition. Blackwell Scientific Publication, Oxford 1979. 2. Herzon FS. Nasal ciliary structural pathlogy. Laryngoscope 1983 93 63-67. 3. Satir P, Sleigh MA. The physiology of cilia and mucociliary interactions. Ann. Rev. Physiol. 1990 52 137-155. 4. Duchateau G, Graamans K, Zuidena J, Merkus FWHM. Correlation between nasal ciliary beat frequency and mucus transport rate in volunteers. Laryngoscope 1985 95 854-859. 5. Liote H. Role of mucus and cilia in nasal...

References

Mucins in the gastrointestinal epithelium a review. Invest. Cell Pathol. 1979 2 195-216. 2. Ehsanullah M, Filipe MI, Gazzard B. Mucin secretion in inflammatory bowel disease correlation with disease activity and dysplasia. Gut 1982 23 485-489. 3. Rhodes JM, Gallimore R, Elias E, Kennedy JF. Faecal sulphatase in health and in inflammatory bowel disease. Gut 1985 26 466-469. 4. Kvietys PR, Granger DN. Regulation of colonic blood flow. Fed. Proc. 1982 41 21002110. 5. Grandison AS,...

Radio controlled capsule

In 1981, a capsule containing a balloon filled with drug was reported, which could be actuated in the gastrointestinal tract when required, by the application of a radio signal89. This technique has been used to study absorption at various sites in the gastrointestinal tract. To locate the capsule, it is swallowed with a small dose of barium sulphate to aid its localisation within the gut and is triggered when required. The absorption of frusemide was compared in 5 subjects using the device90....

Choice of radiolabel

Aqueous phases can be followed using technetium-99m labelled diethylenetriaminepentaacetic acid (DTPA). It is absorbed from the lungs with a half time of about 1 h and rapidly cleared from the body via the kidneys. If prolonged imaging is needed, then a label that clears more slowly from the lung such as 99mTc-labelled albumin should be used. Materials such as 99mTc stannous phytate show better alveolar deposition than pertechnetate or 111In-DTPA with a slow clearance20. It has been...

Drug Delivery Vaginal

Traditionally, vaginally drug delivery was only used for contraceptive agents and also for treatment of local infections. Recently its potential for delivering peptides has been explored since it is vascular, permeable to many drugs5 and drugs absorbed via this route avoid firstpass metabolism. A major problem with using the vagina as a route for systemic drug delivery is that as the epithelium is highly sensitive to oestradiol and its thickness changes throughout the menstrual cycle, so the...

Factors Influencing Drug Retention Proper placement of the eyedrops

Accurate and proper placement of an eye drop may considerably improve the efficacy of drug delivery, as the capacity of the conjunctival sac is dependent on the position of the head and technique of instillation. A drop is placed in the inferior cul-de-sac by gently pulling the lower lid away from the globe and creating a pouch to receive the drop. After gently lifting the lid to touch the globe, a small amount liquid is entrapped in the inferior conjunctival sac, where it may be retained up to...

Preopemtive medication and induction of anaesthesia

Preoperative medication is usually administered parenterally however a more acceptable delivery route, particularly for children, is being sought. Rectal administration of midazolam produced a satisfactory sedative action 30 minutes after administration in children129. Rectal instillation of a solution of midazolam hydrochloride 5 g.L-1 0.3 mg.kg-1 in healthy volunteers produced a bioavailability of about 50 , however metabolic studies suggested that complete rectal absorption of the parent...

Persorption

There is a special mode of permeation across the intestinal wall in which the cell membranes are not involved. Intestinal cells are continuously produced in the crypts of Lieberk hn and migrate towards the tip of the villus. During digestion the cells are sloughed off leaving a temporary gap at the cell apex, and through this gap large particles can slip into the circulation through the intercellular gaps. This process has been termed persorption. The observation that large objects such as...

Absorption Of Drugs Across The Oral Mucosa

The oral cavity is the point of entry for oral drug formulations but usually their contact with the oral mucosa is brief. In order to take advantage of some of the properties of the oral mucosa or to locally treat the mucosa, delivery systems have been designed to prolong residence in this area. The total surface area available for drug absorption is quite limited, being only approximately 100 cm2. Absorption of drugs through the buccal mucosa was first described by Sobrero in 1847 who noted...

Targeting The Oesophagus

In the past attention has been focused on reproducible smooth and rapid oesophageal transit. In some instances, for example in the treatment of oesophageal damage from gastrooesophageal reflux or oesophageal cancer, delivery of drugs to the oesophageal mucosa would be desirable. In 1990, the use of ultrafine ferrite -Fe2O3 , utilising a dye and polymer as an adhesion release controlling delivery system was reported for the delivery of drugs to treat oesophageal cancer39. More recently, poly...

Drug Delivery

A wide range of colonic transit times must be taken into consideration during the design of drug delivery systems. Rapid transit will allow little time for the drug to be released before the dosage form is excreted, whilst prolonged colonic residence may result in the accumulation of drug from multiple doses. After the hepatic flexure, the consolidation of faecal matter gradually increases the viscosity of the luminal contents. This results in increasing difficulty of drug diffusion to the...

Drug absorption from the colon

The transport pathways of the colon allow rapid and specific active bi-directional transport of ions across the epithelial layer. Unlike the small intestine, there are no documented active transporters for organic nutrients in the mature organ and, therefore, no chances for drug molecules to be absorbed in a piggy-back fashion62. The apparent lack of organic nutrient transporters may limit the potential for drug design with respect to carrier mediated transport across the colon, hence drug...

Drug Absorption Through The Vaginauterus

A wide range of drugs have been studied for vaginal absoprtion. These include steroid hormones such as progesterone and oestrogen, prostaglandins, iodides and salicylates5, peanut proteins, bacterial antigens and poly vinyl alcohol m. w. 25,000 Daltons 6. Insulin, hydrocyanic acid, iodides, strychnine, pilocarpine, atropine, quinine and oxyquinolone are rapidly absorbed from cat and dog vaginas5. Quinine and phenol red are absorbed slowly and methylene blue only in very small quantities. A...