Phrmaceutical Formulation - Essay Example

?Pharmaceutical formulation College An emerging technology in the field of pharmaceutical in which prescription is passed through the lungs by the process of inhalation and enters the bloodstream through alveolar epithelium is known as pulmonary drug delivery. With its high efficiency it has proved very useful in today’s medical procedures as it provides an alternative method which seems to be cheaper and acceptable by patients as the risk involved with it is very minimal. It has a wide range of applications, like, levosalbutamol inhalers have been designed to help in the treatment of asthma. Pulmonary drug delivery can be used to administer a vaccine like in the case of currently inhaled measles vaccine given by nebilizer. (Molema, 2001 pg 16) Also it can be used to give medication to infants and young children who have a small tidal volume and low inspiratory flow rates by the use of a baby mask which normally is attached to spacer. (Perry, 2012 pg 25)It has been used to treat lung cancer by the means of inhaled chemotherapy which has proven to be a logical approach and also it is used on patients who are very ill who cannot withstand any more pain by inhaling opioids such as morphine and fentanyl. (Sigmund, 2009 pg10) Drugs used in pulmonary drug delivery have multi-component powders with mucoactive compounds and anti-asthmatic medicines bound together in a single particle because of the mucus layer covering the airways of the tracheobronchial structure. (Friebel, 2010 pg 20)The substances used in the inhalers must dissolve 100% so as not to block the air gaps to avoid suffocation. (Le, 2001 pg 37) Been affected by the rapid change of technology due to great inventions pharmaceutical industries had to do some research to come up with more efficient drug delivery system like drug powder inhalers. (Zeng, 2001 pg 8) Although drug powder inhalers has greatly boosted the pharmaceutical companies there are challenges that are experienced during its formulation like the cohesive ,adhesive property of drug and carrier aggregation, particle size , morphology of the drug and carrier aerosolization performance and powder formulation properties. (Koning, 2001 pg 40)One of the challenges in pharmaceutical industries is to characterize their various physical behaviors; here the concern is mainly focused on the study of the relations relating the properties of the grain to those of the powder bed. (Wang, 2012 pg 44)The goal is thus to be able to control, analyze and improve the manufacturing processes of the powder. (Talton, 1999 pg 60) To improve the aerosolization performance of drug powder inhalers, varieties of carrier and carrier types have to be sampled and studied so as to come up with the best, and the drug ratios are prepared by spray-drying so as to improve the efficiency of the drying procedure and the characterized at last. Again to improve aerosolization two critical physical properties which are the particle size and flowability has to be keenly observed where the particle size should be around 5-6  µm and the angle of repose to be within the ranges of 43°–52° for the flowability to boost the aerosolization. If this is done well the aerosolization performances can be improve greatly. Cohesion forces of particles used in dry powder formulation is a great nuisance to inhalers because it reduces powder flow and hinders accurate metering hence needs to reduce it and this can be achieved by blending the active pharmaceutical ingredient with a larger inert carrier so as to reduce the high cohesion forces that are normally between the micron sized active pharmaceutical ingredient particles. Adhesion forces are also of great concern in dry powder inhalers because if not catered for they make the patient to find it difficult to deliver the drug from the inhaler to his or her system hence it must be overcome or reduced by great magnitude so as to allow liberation of drug from the device with minimal energy from the patient. The particle size is a challenge in drug powder inhalation because a particular size range of particle has to be feed into the inhaler that that can allow it to easily be delivered from the inhaler and at the same time the particle size range should be one that is accepted by the system of the patient without causing any discomfort. This required particle sizes do not exist naturally hence they have to be manually designed and because of their small and fine nature they require advanced technique and the use of sophisticated equipment which might be had to acquire and at the same time are to be operated by highly qualified technicians. Morphology of the drug is usually a challenge because it is very hard to come up with the right requirements as the form and structure of the drug tend to change when it gets in contact with the system of the patience. When drug in powder form is to be delivered to the lungs a device known as dry powder inhaler is used to deliver the dried powder into the lungs hence a dry powder inhaler can be said to be a device that is used to deliver drug in form of dried powder to the lungs. (Pulliam, 2009 pg 50)When it comes to the design of the inhaler a lot of factors has to be considered examples of this include the shape and surface area of the nozzle because when the surface area is too large a lot of powder may be released into the lungs of the patient which will lead to an overdose and if a small surface area is used a small amount of powder will be released to the lungs of the patient causing an under dose which will not effectively help in the tackling of the disease and this will just prolong the suffering of the inhaler user or even worse make the disease to develop resistance towards the drug. Also the patient inhalation flow rate and inhalation maneuver has to be considered because this is not constant to all users. For adults, deposition of drug in the throat due to impaction increases with flow rate but in the case of children the relatively larger size of the tongue and the smaller size of the oral-pharyngeal airway increases deposition for a given volume flow rate. Again in design the appearance of the inhaler has to be considered because this is a device that the user is required to have all time so it must be able to blend in perfectly in the workspace of users and when it comes to children the design has to be eye catching so that they appreciate its beauty and this will improve their morale to use device. Lactose is used as a bulking agent in most of the powder inhalers and also it aids in the uptake of powder from the device during the time of inhalation. When carriers like lactose which has both the large size fraction and the fine size fraction are used in dry powder inhalers, it eases in metering the dose to the user of the inhaler as the large size fraction will help in the ranging processes like; powder flow and fluidization while the fine size faction has been observed to elevate de-agglomeration efficiency of the drug as it is released an advantage that is not exhibited in mannitol. In dry powder inhalers lactose is used to prevent cohesion which is normally one of the factors that brings out challenges during the engineering of a dry powder inhaler. When fine lactose particles and course lactose particles are mixed they tend to improve disaggregation, and at the same time it tend to increase the fine particle fraction of the formulation. Lactose increases the dispersibility and respirable fraction of a dry powder inhaler by the help of the lower energy binding sites on it particles which normally bind the drug (in the inhaler) particle. As far as inhalers uses lactose as bulking agent, its major disadvantage is that it is only suitable to a particular group of people as it cannot be preferred to those with lactose intolerance cause it might pose harm to them although it is documented that the quantity of lactose in inhalers is so small that it cannot cause any serious damage to the body. A process by which dry products are acquired back from an aqueous solution is known as freeze drying and it has been largely used in preparation of inject able pharmaceutical products. For a bulking agent to be used in freeze drying formulation it has to exhibit properties like; good cake supporting properties, readily crystallizes during freeze drying, be able to allow drying processes at higher product temperature and on top of all this, it has to be inert in nature. Freeze dried pharmaceutical products shows the greatest variability when it comes to qualities like size, solid state, shape, fine particle fraction and the dose homogeneity. . (Kho, 2011 pg 54)Freeze dried particles shows the highest powder porosity and smoother surface morphology. Normally there are shortcomings that are associated with drug-carrier dry powder formulation which can be solved perfectly if the technique of freeze drying is accepted fully and employed in the pharmaceutical industry. (Tsukamoto, 2012 pg 76)This will be a very vital step in the industry. The technique can be applied in the late stage purification of pharmaceutical products because it can effectively remove solvents and selectively separate molecules with low molecular weights that are small to be separated by a filtration membrane. (Cheow, 2011pg 100)It has agglomerates that are supposed to detach from carrier sites upon inhalation in the system. After a particle has been subjected to freeze drying technique it becomes more advantageous for inhalation because the particle will have a low density which has came about due to smaller aerodynamics diameter which reduces the probability of deposition by sedimentation or inertial impaction. (KRONBORG, 1966 pg 71) Mannitol has a wide range of application in the field of medicine. It can be used on cerebral oedema to children who are suffering from focal traumatic brain a injury (TBI) that are below the age of 15 years as it has proven to be more effective on them and has no serious side effects towards them. (Australia, 1970 pg 13) It has a broad application when it comes to clinical procedures like it can be used in the management of raised intracranial pressure (ICP), for renal fortification in cardiac, vascular, and renal during surgical procedures, and in the supervision of rhabdomyolysis. It has also been used in the previous times for bowel preparation before colorectal surgery. (Henstra, 2000 pg 49) When administered with other diuretics in the body it helps in removing or reducing certain drug poisons that come about due to misusing of the drug. Sometimes mannitol is given to children as laxative because it can act as an osmotic laxative. If allowed to form a complex with boric acid it will enhance the acid by increasing its strength. Mannitol is about 50 percent as sweet as sucrose with a desirable cooling effect often used to disguise bitter tastes. It is non-cariogenic with a low caloric content. (Dox, 1917 pg 80)Being an isomer of sorbitol it is typically produced by the hydrogenation of specialty glucose syrups making it commercially available in variety of powder and granular forms. When mannitol is co-crystallised together with lactose it can be used as carriers in formulation for dry powder inhalers using engineered mixtures of the two components. A glucocorticoid steroid that is used for the treatment and prevention of nasal polyposis and also for treatment of asthma and non-infectious rhinitis is known as budesonide. Budesonide has a broad area of application; like, it is used to help in controlling the symptoms of asthma and hinders asthma attacks by minimizing the swells in the airways of the lungs. (Dahl, 1998 pg 51)It achieves this by helping in controlling the asthma and relieving asthma symptoms by keeping the airways open hence making breathing easier. (Magnussen, 2003 pg 40)Budesonide is known to cause hypersensitive reaction to some of its uses like rash, angioedema, and bronchospasm. Physicians should consider information about individual sensitivity to effects on cortisol production which arises from budesonide when prescribing this drug. (Johansson, 1983 pg 76)Because of an esterification process which increases budesonide lipophilicity it has been documented that it is retained much long in the airway than other ICS. When combined with delivery devices it acquires favorable efficacy and tolerability profiles. . Budesonide liposomes composes of egg phosphatidhyl choline and cholesterol which are prepared by the process of lipids film hydration technique and modeled into the desired size of approximately less than 5 ?m. A rapid method is used in the separation of free drug by centrifugation at a lower centrifugal force. Liposomal dispersal is subjected to lyophilization after been blended BUD with cryoprotectant in varying bulk and mass ratios, and percent drug remaining entrapped after lyophilization was optimized. A comparative drug retention study on storage of DPI formulations is then carried out according to standards. The most abundant phospholipids in animal and plants are D-a-phosphocholine dipalmitoyl amounting to almost 50% of the total phospholipids and this makes it a key building block of membrane bilayers. In animal tissues D-a-phosphocholine dipalmitoyl tends to exist mainly in the diacyl form, but small proportions of alkylacyl and alkenylacyl forms may also be present. Compared to other zwitterionic phospholipids, D-a-phosphocholine dipalmitoyl tend to contain lower proportions of arachidonic and docosahexaenoic acids and more of the C18 unsaturated fatty acids. Its main use is stabilizing or regulating the structure of the chromatin, as well as being a source of diacylglycerols with a signaling function. When it comes to psychological conditions it is an important element because it is necessary for normal secretion of the plasma lipoproteins. (Adjel, 1997 pg.23). In the nerves tissue for production of acetylcholine, this is a neurotransmitter which is of importance to learning, memory and sleep activities. D-a-phosphocholine dipalmitoyl is easily isolated by thin layer or high performance liquid chromatography methods. From the range of strong acids to the range of strong alkaline over a pH range, it exists as a neutral solution and this has enabled it to be widely mixed with different carriers without the risk of worrying about acid-base reaction. (Johnson, 2011 pg 48) Also because of its neutral nature over a large range on the pH chart it has been used in dry powder inhalation to adjust the acidity or the basic content of the powder to be delivered to the respiratory system of the user to the required concentration. With the high protein level that is found in leucine it has made it possible for leucine to be widely used in the pharmaceutical industry. Some of the application are that they can be included as one of the mixing component when a pharmaceutical company wants to come up with a prescription that may help in weight management because leucine will act as a hunger controller due to its high protein level. (Pajari, 1984 pg 68) Leucine prevents or restores muscle degeneration when administered to patients suffering from liver diseases as it tends to increase the nitrogen balance. When the dry powder inhaler is meant to be used to create or bring back the appetite of the user leucine is used as the dried powder because of its ability to add flavor. Athletes require nutritional supplements for them to survive and be able to compete as the best and they do this by the help of leucine which can provide the extra energy. (Chevalier, 2002 pg 59)One of the properties that it has that poses a threat to the users is that, it is only degraded in tissues outside the liver and alteration in its degradation process can cause a genetic disorder which might be very hard to overturn. In dry powder formulation leucine is used to boost the flow rate because it is able to provide extra energy and at the same time it helps in boosting the aerosolition of the drug that is administered. This has greatly improved the time that it takes for the drug to reach the whole body. With the three hydroxyl groups that are responsible for the glycerin solubility in water and its hygroscopic nature, the glycerine backbone being central to lipids, sweet tasting and low level of toxin that it deposits to the blood system has made it possible for the glycerine to be useful in many areas when it comes to clinical duties. It is used in drinks to bring out the sweetness taste of the beverage and at the same time serves as a preservative of the drink. It as properties almost to that of diesel hence it can be used as diesel substitute. In theaters acts has used it to bring out illusion of tears by applying it on their faces. Nitroglycerin being an essential in smokeless gun powder has been produced in artillery bases by the use of glycerine on of the raw materials. (Jungermann, 1991 pg 100) Glycerine has the ability to completely dissolve in water and alcohols; it is slightly soluble in ether, ethyl acetate, and dioxane but insoluble in hydrocarbons. Because to its three hydroxyl groups glycerine has the useful solvent properties similar to those of alcohol and water and this has enabled it to be a useful solvent to many solid organic and inorganic hence a useful material in the field of pharmaceutical. (Chalmers, 1918 pg 81) Because of its high viscosity and ability to remain fluid at low temperatures it can be used naturally as a lubricant. In dry powder formulation they are smeared along the delivery system of powder blends to hinder the adherence of powder on the surfaces. (Woollatt, 1985 pg 27) Poly(D,L-lactide-co-glycolide) which can be abbreviated as PLGA, has a wide range of application when it comes to the field of pharmaceutical industry because of the characteristics of its nature, that is, it is biocompatible and biodegradable, it exhibits a wide range of erosion times, also has tunable mechanical properties and most importantly, it is an approved polymer. Because of its degradation level it can be used for sustained drug release at desirable doses by implantation without surgical procedures and also PLGA is used as a delivery vehicle for various drugs and for presenting antigens to dentritic cells for vaccination, proteins and other macromolecules in commercial use and in research. PLGA can accommodate molecules of nearly any size because they have the ability to be processed into almost any shape and size. The successful nature of PLGA as a biodegradable polymer is due to the fact that it produces original monomers as it undergoes hydrolysis in the body. (Weidenauer, 2000 pg 52)PLGA particles offer considerable flexibility when it reaches a point of delivery to the body as they have shown that they can be effective when presented to the body by the mode of injection through the muscle tissues as compared to when they are delivered orally. Fabricating the desired particle to be used in the inhalers has proved to be a setback for PLGA and this has limits its use in dry powder delivery. In dry powder inhaler formulation PLGA can be used to breakdown the particle of the powder to be used. Bibliography (1996). Leucine zippers. London, Academic Press. ADJEI, A. L., & GUPTA, P. K. (1997). Inhalation delivery of therapeutic peptides and proteins. New York, M. Dekker MOLEMA, G., MEIJER, D. K., MANNHOLD, R., KUBINYI, H., & TIMMERMAN, H. (2001). Drug Targeting Organ-Specific Strategies. Methods and Principles in Medicinal Chemistry. Wiley VCH. http://www.myilibrary.com?id=64441 SIGMUND, W. (2009). Particulate systems in nano- and biotechnologies. Boca Raton, CRC Press FRIEBEL C., & STECKEL H. (2010). Single-use disposable dry powder inhalers for pulmonary drug delivery. Expert Opinion on Drug Delivery. 7, 1359-1372 PERRY, A. G., POTTER, P. A., & ELKIN, M. K. (2012). Nursing interventions & clinical skills. St. Louis, Mo, Mosby LE BRUN, P. P. H. (2001). Optimization of antibiotic inhalation therapy in cystic fibrosis: studies on nebulized tobramycin : development of a colistin dry powder inhaler system. Thesis (doctoral)--Rijksuniversiteit te Groningen, 2001. ZENG, X. M., MARTIN, G. P., & MARRIOTT, C. (2001). Particulate interactions in dry powder formulations for inhalation. London, Taylor & Francis. KONING, H. D. (2001). Dry powder inhalation: technical and physiological aspects, prescribing and use. S.l, s.n.]. TALTON, J. D. (1999). Pulmonary targeting of inhaled glucocorticoid dry powders. Thesis (Ph. D.)--University of Florida, 1999. WANG, Y., KHO, K., CHEOW, W., & HADINOTO, K. (2012). A comparison between spray drying and spray freeze drying for dry powder inhaler formulation of drug-loaded lipid-polymer hybrid nanoparticles. International Journal of Pharmaceutics. 424, 98-106. PULLIAM, B. L. (2009). Nanoparticle vaccines by inhalation. Thesis (Ph.D., Dept. of Biophysics)--Harvard University, 2009. KHO, K., & HADINOTO, K. (2011). Optimizing aerosolization efficiency of dry-powder aggregates of thermally-sensitive polymeric nanoparticles produced by spray-freeze-drying. Powder Technology. 214, 169-176 TSUKAMOTO M., HIGUCHI Y., KAWAKAMI S., YAMASHITA F., HASHIDA M., OKUDA T., & OKAMOTO H. (2012). Bovine serum albumin as a lyoprotectant for preparation of DNA dry powder formulations using the spray-freeze drying method. Biological and Pharmaceutical Bulletin. 35, 1178-1181. CHEOW, W., NG, M., KHO, K., & HADINOTO, K. (2011). Spray-freeze-drying production of thermally sensitive polymeric nanoparticle aggregates for inhaled drug delivery: Effect of freeze-drying adjuvants. International Journal of Pharmaceutics. 404, 289-300. KRONBORG, O. (1966). The influence of mannitol on renal function in major surgery. An investigation of 50 patients subjected to stomach and gallbladder operations. Stockholm, Norstedt. AUSTRALIA. (1970). Sorbitol and mannitol. Canberra, Commonwealth Govt. Print. Off. (n.d.). Global Trade Perspective 2005 - Mannitol. Business Source Complete. San Diego, ICON Group International, Inc. http://proxy.library.carleton.ca/login?url=http://search.ebscohost.com/direct.asp?db=bth&jid=%221TJC%22&scope=site&site=bsi. HENSTRA, S. A. (2000). The mannitol phosphotransferase system of Bacillus stearothermophilus. S.l, s.n.]. DOX, A. W., & PLAISANCE, G. P. (1917). The occurrence and significance of mannitol in silage. Ames, Iowa, Agricultural Experiment Station, Iowa State College of Agriculture and Mechanic Arts. (1989). Budesonide nebulising suspension. Oxford Clinical Communications. OXFORD CLINICAL COMMUNICATIONS, & ASTRA USA. (1994). Rhinocort (budesonide) nasal inhaler: workbook. Oxford, Oxford Clinical Communications on behalf of Astra USA. DAHL, R. (1998). Beclomethasone diproportionate and budesonide: the clinical evidence reviewed. London [u.a.], Saunders. MAGNUSSEN, H. (2003). Budesonide modulite: improving the changeover to CFC-free treatments. London, Saunders. JOHANSSON, S.-A. (1983). Evaluation of budesonide: a new glucocorticosteroid for local treatment of bronchial asthma. Lund, Rahms. CAMERON, D G, CASAL, H L, MANTSCH, H H, BOULANGER, Y, & SMITH, I C. (n.d.). The thermotropic behavior of dipalmitoyl phosphatidylcholine bilayers. A Fourier transform infrared study of specifically labeled lipids. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1327498. JOHNSON, M. A. (2011). Near-field investigations of the anisotropic properties of supported lipid bilayers. Thesis (Ph.D.) -- Purdue University, 2011. http://hdl.handle.net/1805/2863. RUSTOW, B, SCHLAME, M, HAUPT, R, WILHELM, D, & KUNZE, D. (n.d.). Studies on the formation of dipalmitoyl species of phosphatidylcholine and phosphatidylethanolamine in pulmonary type II cells. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1130800. JUNGERMANN, E., & SONNTAG, N. O. V. (1991). Glycerine: a key cosmetic ingredient. New York, Marcel Dekker. WOOLLATT, E. (1985). The manufacture of soaps, other detergents, and glycerine. Chichester, E. Horwood. GLYCERINE PRODUCERS' ASSOCIATION. (1941). Glycerine facts. New York, N.Y., The Association. CHALMERS, T. W. (1918). The production and treatment of vegetable oils, including chapters on the refining of oils, the hydrogenation of oils, the generation of hydrogen, soap making, the recovery and refining of glycerine, and the splitting of oils. London, Constable & company ltd. GLYCERINE PRODUCERS' ASSOCIATION. (1963). Uses of glycerine. New York, Glycerine Producers' Association. GLYCERINE PRODUCERS' ASSOCIATION. (1939). Glycerine and its derivatives. WEIDENAUER, U. (2000). Feasibility study for the microencapsulation of Pamidronate-disodium using D,L-Poly(lactide-co-glycolide acid-glucose): evaluation of different techniques and devices. Marburg, Go?rich & Weiersha?user PAJARI, M. (1984). Transport of leucine, isoleucine and valine and their incorporation into protein in rat brain. Tampere, University of Tampere. CHEVALIER, D. (2002). Molecular analysis of STRUBBELIG, a putative leucine rich repeat receptor like kinase involved in the control of cell proliferation in Arabidopsis thaliana. Thesis (doctoral)--Universita?t Zu?rich, 2002. Read More