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

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...

X

Vaccines A suspension of infectious agents or part of them administered for the purpose of establishing resistance to an infection. Vagus The 10th cranial nerve. It is a mixed nerve with both motor and sensory functions. Vasoactive intestinal peptide (VIP) Peptide present in the mucosa of the gastrointestinal tract with the main function of inhibiting gastric function and secretion. Vasopressin Hormone formed in the hypothalamus. It has an antidiuretic effect and pressor effect that elevates...

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...

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...

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...