Pharmacokinetics Of Inhalation Aerosols Implications For Cancer Treatment

The absorption and distribution of drug following deposition of the aerosol particles in the airways is a complex process. However, it is of paramount importance to understand the dynamics of drug fate in order to achieve optimal efficacy of chemotherapeutic agents. Much information on the fate of inhaled drugs has been obtained from asthma medications that have been investigated extensively (114), though recently a great amount of research on this topic has arisen due to the interest in using...

Spiros

The Spiros insulin consists of a dry powder inhaler and blisterdisks. The blisterdisks contain a preparation of 11 micronized insulin crystals blended with lactose monohydrate NF. The blend is filled into blisterdisks at a target fill weight of 9.5 mg per well. This results in 1.05 mg of insulin in each blister well that is equivalent to 30 units. The median aerodynamic particle size of the insulin crystals is 2-3 m and the median size of the lactose particles is 150 m. The inhaler is a hand...

Factors Affecting Nasal Absorption

A combination of the structure and function of the nasal mucosa as a barrier to absorption, the properties of the active drug and the formulation within which it is contained will affect the extent to which a compound is absorbed nasally. The following factors are commonly reported as significantly influencing the extent of nasal absorption. Generally, drugs which are in solution will be rapidly absorbed nasally (31), although it appears that hydrophilic compounds are not readily absorbed above...

Polymer Implants

Cancer chemotherapy is not always effective. Difficulties in drug delivery to the tumor, drug toxicity to normal tissues, and drug stability in the body contribute to this problem. Polymeric materials provide an alternate means for delivering chemotherapeutic agents. When anticancer drugs are encapsulated in polymers, they can be protected from degradation. Implanted polymeric pellets or injected microspheres localize therapy to specific anatomic sites, providing a continuous sustained release...

Controlled Release Microparticles

Different types of anticancer drugs have been incorporated into biodegradable microparticles (62-69). Compared to implants these systems offer the advantage that they can be injected directly into the wall of the resection cavity (the neighboring tissue of the debulked tumor) at multiple positions. As drug transport within the brain tissue is generally restricted to a few millimeters, this type of devices allows to more easily cover larger brain regions. For instance, Emerich et al.(67)...

Hypertension

Hypertension (high blood pressure) is considered to be one of the major medical problems of the world. In the United States nearly 25 million cases are diagnosed each year. Research shows that effective control of high blood pressure can reduce associated morbidity (notably stroke, kidney, and congestive heart failure) and prolong life. It may be argued whether hypertension is a disease or merely a risk factor towards disease. Nevertheless, hypertension increases the chance of developing organ...

Class lA Antiarrhythmic Agents

Procainamide hydrochloride monohydrochloride. It was developed in the course of research for compounds structurally similar to procaine, which had limited effect as an antiarrhythmic agent because of its central nervous system side effects and short-lived action resulting from the rapid hydrolysis of its ester linkage by plasma esterases. Procainamide hydrochloride is also more stable in water than procaine because of its amide structure. Metabolism of procainamide hydrochloride occurs through...

Overcoming Severe Systemic Side Effects Pharmacokinetic Advantage

The severe systemic side-effects experienced by patients during lung cancer chemotherapy have the dual disadvantage of limiting the effectiveness of therapeutic regimens while significantly decreasing the patient's quality of life (16,17). During therapy, the delicate balance between patient tolerability and effectiveness of intravenously infused chemotherapy must be rigorously maintained, and any deviations can result in sub-optimal treatment. As a means of overcoming this obstacle, it would...

Paclitaxel

Taxanes (paclitaxel, docetaxel) are chemotherapeutic agents used to treat a variety of malignancies including breast cancer, ovarian cancer, non-small cell lung cancer and prostate cancer. As discussed previously in this chapter, physicochemical properties of taxanes (poor solubility) necessitates the inclusion of surfactant vehicles (Cremophor , Tween 80) in commercial formulations containing these medications. In addition to influencing the pharmacokinetic profile of cancer drugs, these...

Future And Clinical Translation

Presently, lung cancer accounts for approximately one-third of cancer deaths, of which the vast majority of patients present or develop advanced lung cancer, and ultimately experience a rapid demise. Early trials with chemotherapy in NSCLC were quite disappointing, exhibiting a response rate of around 10-15 , and an approximate 5 week prolonged survival relative to supportive care. Moreover, in many cases chemotherapy regimens were found to be associated with worse results than supportive care...

Attention DeficitHyperactivity Disorder

Attention-deficit hyperactivity disorder (ADHD) is a common neurobeha-vioral disorder that is often recognized in early childhood, and can persist into adulthood. The principal characteristics of ADHD are inattention, hyper-activity, and impulsivity. In the United States, between 3 and 6 of school-aged children meet accepted diagnostic criteria for ADHD (183). Over 60 of children with a diagnosis of ADHD continue to exhibit ADHD symptoms through their adult life (184). Methylphenidate (MPH), a...

Candida Infections

Candida can cause both exogenous and endogenous endophthalmitis. Candidal exogenous endophthalmitis is comparatively rare and usually occurs following eye surgery (keratoplasty, cataract extraction), traumatic ulcers, and contaminated ophthalmic irrigation solutions (117). Candida spp. commonly causes endogenous endophthalmitis particularly in the retina producing both retinal and vitreal lesions (118). It also causes cotton wool spots and white centered hemorrhages. Sometimes it can affect the...

Cancer Therapy

Solid dispersion technologies have also been explored for improving drug therapies for the treatment of various conditions associated with cancer. Many anticancer drugs have poor aqueous solubility characteristics that preclude the efficacy of traditional oral dosage forms. Therefore, these drugs are commonly administered to the patient as parenteral injections. Since intrusive methods of drug administration are inconvenient and undesirable for the patient, there would be substantial benefit to...

Microparticles Nanoparticles Nanofibers and Nanotubes

The use of microparticles (> 1 m) and nanoparticles (< 1 m) as delivery vehicles for anticancer therapeutics has great potential to revolutionize the future of cancer therapy. Microparticles have been used a carrier system for anticancer drugs using different types of polymers, such as poly(d,l-lactic-co-glycolic acid) (PLGA). For example, sustained-release anastrozole-loaded PLGA microparticles have been developed for the long-term treatment of breast cancer (73). Nanoparticles have been...

References

Toxicological implications of nasal formulations. Drug Del 1999 6 227-42. 2. Junginger HE. Bioadhesive polymer systems for peptide delivery. Acta Pharma Technol 1990 36 110-26. 3. Cauna N. Blood and nerve supply of the nasal lining. In Procter DF, Anderson I, eds. The Nose, Upper airway Physioogy and the Atmospheric Environment. Amsterdam Elsevier Biomedical Press 1982 45-66. 4. Behl CR, Pimplaskar HK, Sileno AP, de Meireles VD, Romeo VD. Effects of physicochemical...

Advanced Formulations Targeting the Oral Cavity

Advantages of targeting the oral cavity include the relatively large surface area for drug absorption the total surface area is approximately 170 cm2 with the buccal membranes being approximately 50 cm2 of this total area (2) and the ready accessibility of this site. The rich blood supply of the oral cavity is also advantageous for systemic absorption of drugs as well as the low metabolic activity within the mouth compared to the remainder of the GI tract. In the treatment of local infections...

Non Invasive CNS Drug Delivery

Compound lipophilicity is a fundamental physicochemical property that plays a pivotal role in the absorption, distribution, metabolism, and excretion (ADME) of therapeutic agents. A parabolic relationship often exists between measured lipophilicity and in vivo brain penetration of drugs, where those moderate in lipophilicity often exhibit highest uptake (45). One Table 2 General Approaches to Enhance CNS Drug Delivery Table 2 General Approaches to Enhance CNS Drug Delivery Transdermal drug...

Types of Arrhythmias

Sinus tachycardia is an arrhythmia originating in the SA node (10,11) characterized by rate of over 100 beats per minute. Sinus tachycardia may caused by numerous conditions such as fever, hypotension, heart failure, thyrotoxicosis, stimulation of the sympathetic nervous system, and life style drugs such as alcohol, caffeine, and nicotine. Treatment of sinus tachycardia (6,10) should be directed towards identifying the underlying cause of the arrhythmia. The P, QRS, and T deflection are all...

Invasive Drug Delivery

In recent years, various strategies have been designed to circumvent the BBB. Transient BBB disruption and osmotic BBB disruption are such strategies, and have been studied extensively in preclinical and clinical studies. After the BBB is being weakened, drugs can undergo enhanced extravasation rates in the cerebral endothelium, resulting in increased parenchymal drug concentrations. A variety of techniques that transiently disrupt the BBB have been investigated, such as administration of...

The Oral Cavity Infections of the Oral Cavity

Infections of the oral cavity are often caused by overactivity of endogenous flora (e.g. dental caries) and also by primary pathogens (e.g. candidiasis). Typical disorders include viral infections such as Herpes simplex (cold sores) fungal infections such as oral thrush caused by the Candida albicans and other Candida species bacterial-induced infection such as gingivitis leading to periodontitis in some cases. Standard treatments for oral infections are systemic administration of antifungal or...

Lung Cancer

Despite the decades of awareness, and the introduction of newer therapies and treatment regimens, overall lung cancer survival rates remain low, and the urgency of replacing conventional approaches with novel or combination therapies exhibiting enhanced anti-cancer efficacy is now being recognized. The most telling statistic regarding lung cancer is that the annual number of deaths attributed to this disease continues to rise with each passing year (Fig. 1). This dual lack of success in both...

Budesonide

Eudragit Microparticles

Budesonide (BDS) is a structural analog of the naturally occurring mineralocorticoid, cortisone, produced by the adrenal glands. The chemical structure of budesonide is depicted in Figure 1. This drug was determined not to have the undesirable side effects of water retention, high blood pressure, and muscle weakness associated with other glucocorticoids like cortisone. Budesonide is most often given by oral, topical, and pulmonary administration. Budesonide has been used to treat a number of...

Survey Of Glucody Products In Indian Market

Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002 106(25) 3143-421. 2. Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 1998 339 (4) 229-34. 3. Centers for Disease Control...

Advanced Formulations Targeting the Esophagus

Infections of the esophagus are primarily associated with immunocompro-mised hosts, including patients undergoing cancer chemotherapy or those with HIV. Available antifungals for the treatment of esophageal candidiasis include polyenes, azoles, nystatin, and AmB. Therapy with these agents is not always successful due to the poor permeation of the esophagus and their low systemic availability. The treatment of choice is fluconazole 100-200 mg daily which will achieve endoscopic clearance in more...

Class IB Antiarrhythmic Agents

Lidocaine hydrochloride. 2-(Diethylamino)-2',6'-acetoxylidide monohydro-chloride. This drug was conceived as a derivative of gramine (3-dimethyla-minomethylindole) and introduced as a local anesthetic, is now being used intravenously as a standard parenteral agent for suppression of arrhythmias associated with acute myocardial infarction and cardiac surgery. Lidocaine is the drug of choice for the parenteral treatment of premature ventricular contractions. Lidocaine hydrochloride administration...

Fungal Keratitis

This form of keratitis is frequently caused by filamentous fungi such as species of Fusarium, Aspergillus and Curvularia, and by yeast-like fungi such as Candida (107). The symptoms include blurred vision, red and painful eye, increased sensitivity to light, and excessive tearing or discharge. Clinically, it is often difficult to differentiate between fungal and bacterial infections. Diagnosis can be done by corneal culture, tissue biopsy or confocal microscopy (108). The commonly used...

Ideal Pulmonary Delivery of Insulin

The concept of inhaled insulin was first introduced in 1925 where it was studied in five diabetic patients (18). Variability in bioavailability and system portability made pulmonary insulin delivery at the time unfeasible. Interest in pulmonary delivery resurfaced in the 1970s and 1980s in the clinical setting (19). With the advancements in drug delivery technology, the pulmonary delivery of insulin became more viable. Pulmonary delivery of insulin is ideal due to the large surface area of the...

Itraconazole Prophylaxis

Itraconazole Fungal Infections

Although prophylactic use of fluconazole is safe and effective in preventing invasive candidiasis, this strategy is ineffective against invasive aspergillosis. Many transplant centers have instituted prophylactic strategies utilizing agents with activity against Aspergillus species such as itraconazole secondary to the high morbidity and mortality rates associated with invasive aspergillosis in high-risk immunocompromised patients. In a Figure 2 Percent of patients who developed invasive fungal...

Recent Advances in Nebulizer Technology

Nebulizers have been used for asthma therapy for many years and are used for the delivery of fine droplets of drugs to the lungs. For this reason they have been optimized for aerosol delivery in the upper range of inhalation Figure 21 Median adhesion between an albuterol particle and the internal walls of five pMDI canisters in model propellant using colloid probe microscopy. Canister coatings were as follows Aluminum ALU , anodized aluminum AN-ALU , polytetrafluoroethylene PTFE , fluorinated...

Formulation of pMDI Systems

Modified Release Medication

Advances in Suspension-Based pMDI Systems Due to the poor solvent properties of HFAs, suspension based systems are a popular formulation route for current pMDIs. In general, research in this area has focused on two main themes over the past 5 years particle engineering and the application physical stabilizers. As with DPI systems, the drug particles used in suspension based systems should ideally have a diameter of less than 6 m to achieve a therapeutic affect upon administration. As previously...

Fexinidazole Preformulation Study Results.

See ATP-binding cassette ABC Abraxane , 205 Absorption enhancers, 286 ABT-963, 462 Accelerated idioventricular rhythm, 368 ACG. See Acycloguanosine ACG Active pharmaceutical ingredient API powder, DPI technology, 5 API modification to improve respiratory deposition, 17-21 Active vibrating mesh ultrasonic nebulizers, 39 ACV. See Acyclovir ACV Acycloguanosine ACG , 148 Acyclovir ACV , 147-149 Adaptive aerosol delivery technology, 38 Adenocarcinoma, 82 Adenosine, 375 Adenovirus infections,...

Doxorubicin

Novel Liposomal Herbal Drug Formulation

Doxorubicin is an anthracycline antibiotic used to treat various cancers including breast, ovarian and lung cancer. While anthracyclines are among the most effective chemotherapeutic agents in the treatment of numerous Table 5 Advanced Formulation Strategies Examples of Drug Products Used to Treat Cancer Pegylated liposomal doxorubicin Nanoparticle doxorucin Surfactant-free formulation that prolongs circulation time, lowers drug distribution to healthy tissues, promoting tumor uptake...

Aerosol Delivery To Treat Lung Cancer

To date, reports of aerosolized chemotherapy for the treatment of lung cancer and pulmonary metastases have been quite limited. Table 1 summarizes all known studies that have investigated local lung delivery of anticancer agents including cytotoxics, gene therapy, chemopreventative agents, Benzotaph, endoxan, thiophosphamid, cyclophosphan Mitomycin-C FU Liquid aerosol Intratracheal instillation Human 8 58 showed tumor disappearance, 6 58 significant reduction 1 of the 4 patients showed...

Beclomethasone and Betamethasone

Beclomethasone and betamethasone are two very closely related glucocorticoid immunosuppressants with identical structures, except in betamethasone, the heteroatom substituent on the steroidal backbone is fluorine 12 , while in beclomethasone, the heteroatom substituent is chlorine 13 . The chemical structures of beclomethasone and betamethasone dipropionate are depicted in Figure 1. Frequently, these two drugs are administered as salt forms dipropionate, sodium phosphate due to their low...

Exubera System

Exubera is the first Food and Drug Administration approved inhaled insulin product. It is approved for the treatment of adult patients with T1DM and T2DM 22 . Exubera is currently available in a short acting formulation to control post prandial glucose excursions. In patients with T1DM, Exubera should be used in combination with long acting insulin, which provides basal insulin replacement. In patients with T2DM, Exubera can be used either as monotherapy or in combination with long acting...

Methods For Enhancing Nasal Absorption Absorption Enhancers

The use of absorption enhancers in the formulation is a commonly employed method for increasing absorption of substances across the nasal mucosa. Many reports on the use of absorption enhancers have shown positive results, although it is often unclear whether or not long term use will result in harmful side effects to the nasal mucosa. Bile salts have often been investigated as absorption enhancers and are possibly the most widely used means of aiding absorption via use of a surfactant 49 ....