By W. Bernado. Warner Pacific College. 2019.
In the case of nanospheres buy discount avana doctor who cures erectile dysfunction, where the drug is uniformly distributed cheap avana on line erectile dysfunction jelly, the release occurs by diffusion or erosion of the matrix under sink conditions discount 100 mg avana with amex erectile dysfunction shake recipe. If the diffusion of the drug is faster than matrix erosion, the mechanism of release is largely controlled by a diffusion process. The rapid initial release or “burst” is mainly due to drug particles over the surface, which diffuse out of the drug polymer matrices (3). Kinetics of Drug Release from Micro/Nanoparticles Kinetics of drug release is an important evaluation parameter. The knowledge of the mechanism and kinetics of drug release from these microparticlulate systems indicates their performance and gives proof of adequateness of their design. Drug release data is applied basically for (i) quality con- trol; (ii) understanding of physicochemical aspects of drug delivery systems; (iii) understanding release mechanisms; and (iv) predicting behavior of systems in vivo. However, there are difﬁculties in modeling drug release data, as there is a great diversity in the physical form of micro/nanocapsules/particles with respect to size, shape, arrangement of the core and the coat, properties of core-like solubil- ity, diffusivity, partition coefﬁcient, properties of coat-like porosity, tortuosity, thick- ness, crystallinity, inertness, etc. In addition, there are problems in translating kinet- ics of drug release from “micro” products of perfect geometry to various irregular micro/nanosystems (4). Factors Inﬂuencing Drug Release There are various factors that inﬂuence drug release, discussed as follows: 1. Permeation: It is the process whereby the drug is transported through one or more polymeric membranes corresponding to the coating material which acts as the barrier to drug release. Permeation depends on crystallinity, nature of polymer, degree of polymerization, presence of ﬁllers and plasticizers, matrix properties such as thickness, porosity, tortuosity, diffusion layer, etc. Per- meation may be reduced by the incorporation of dispersed solids, ﬁllers, waxy sealants, and others. Diffusion: It is the movement of drug across concentration gradient until equal- ization takes place. Diffusion coefﬁcient (D) is a measure of the rate of drug movement Diffusion coefﬁcient (6) depends on various factors such as (i) tempera- ture (Arrhenius equation); (ii) molecular weight of the molecule; (iii) radius (for small, electrically neutral, spherical molecules); (iv) plasticizer concentration; (v) size of the penetrant, (vi) position of the drug in the microsphere; and (vii) inter- action between the polymer and the drug. Partition coefﬁcient: Partition coefﬁcient between polymer solvents is referred to as Ko/w. Drug solubility: As diffusion depends on concentration gradient, drug solubility in the penetrant becomes important and then drug release becomes dissolution dependent for sparingly soluble drugs. The Noyes-Whitney equation (8) dC = k(Cs − C dt where dC/dt = amount of drug released per unit time; k = dissolution rate constant; Cs = saturation solubility in solvent; C = concentration in solvent at time t; and Ds A k = (6) Vlb where Ds = diffusion coefﬁcient of the solvent; V = volume of the solution; and lb = boundary layer thickness. By substituting the value of k in equation (5), we get dC Ds A = (Cs − C dt Vlb thus, water-soluble drugs will be released faster than the hydrophobic ones. Si-Nang and Carlier (9) modiﬁed this equation for drug release from micro- capsules dC Ds A K = (8) dt Vlm where A = internal surface area of coating. In this case, the plot of 3 W versus t gives a straight t line and the value of k can be obtained from the slope. For weakly acidic and basic drugs, the inﬂuence of pH on solubility is given by the Handersson-Hasselbach equation: S − S0 For weak acids, pH = pka + log (10) S0 S0 For weak base, pH = pka + log (11) S − S0 where S = saturation solubility of the solute; S0 = intrinsic solubility of the solute. In addition, ﬂux ∝ 1/l; so, as the thickness decreases, ﬂux also increases due to reduced diffusional path length. Other factors include type and amount of matrix material, size and density of the microparticle, presence of additives or adjuvants, extent of polymerization, denaturation, cross-linking or hardening, diffusion temperature, diffusion medium, its polarity, presence of enzymes, etc. Empiric Models of Drug Release Kinetics of drug release from microparticulates can be understood from various models based on their nature. However, simple empiric models are often used in place of complex models, which are discussed in the following text. Exponential Equation Diffusional exponent approach has been given by Peppas and colleagues (11,12). It is applicable for hydrating or eroding systems in which D is not constant, thereby giving anomalous diffusion. Mt n = kt (12) M0 where Mt/M0 = fractional mass of drug released at time t; and n = diffusional expo- nent. The two exponents consist of rapid or burst phase and slow or sustained release phase, respectively. On converting equation (15), we get In Mt 3k1t 1 − =− 2 M0 r which is the equation for a straight line. Nowadays, drug release kinetics are determined and better understood from their nature, depending on whether they are reservoir-, matrix-, or sandwich-type systems. Reservoir-Type Devices (Microcapsules) (14–18) Various equations have been given depending on different situations. Case 1 Assuming that thermodynamic activity of the core material is constant within the microcapsule, which is spherical and has inert homogeneous coating, steady-state release rate is derived from Fick’s ﬁrst law of diffusion. However, when the ratio of ro to ri is 4, further increase in size will not signiﬁcantly affect drug release (14). If product is tested immediately after preparation, as ﬂuid takes time to pene- trate and attain concentration gradient, there will a delay or lag time, t1 is given by Crank’s equation as, t = (r − r )2 6D (22) 1 o i This can be used to ﬁnd D at a particular time, and vice versa, if ﬁlm thickness is known. If the product is stored for a long period of time before testing or has surface- associated drug, it shows burst effect, leading to the initial overdosage. Thus, the time necessary to reach steady state depends on coating thick- ness and D. The burst time, tb,is 2 (ro − ri) tb = (23) 3D Monolithic Devices (Microparticles) (19–22) Monolithic or matrix systems are those in which the core is uniformly dispersed throughout the matrix polymer. The drug release kinetics will depend on whether the drug is dissolved or dispersed in the polymer. Early stage approximation is given by the Baker-Lonsdale equation (14): 1/2 Mt Dt 3Dt = 6 2 − 2 (24) M∞ r r where M∞ = drug dissolved in the polymer; Mt = drug released at time t; r = radius of particle; and D = diffusion coefﬁcient. Then, the equation will convert to Mt = − 3 (25) M0 Total drug release can be obtained by the integration of the equation: 1/ d(Mt/M∞) D 2 3D = 3 2 t − 2 (26) dt r r This is the equation for a straight line and shows that release is inversely propor- tional to the radius, r, of the microparticles. Later time approximation is given as follows: 2 Mt 6 Dt = 1 − 2 exp 2 (27) M∞ r which is valid for (Mt/M∞) > 0. Inte- gration of the equation gives 2 d(Mt/M∞) 6Dt Dt = 2 exp − 2 (28) dt r r Thus, it shows that later drug release is exponential. Case 2 When the drug is dispersed in the coat, that is, the drug is insoluble in and is uni- formly dispersed throughout the matrix A. The Baker-Lonsdale equation derived from the Higuchi equation for homoge- neous, spherical matrix 1 d(Mt/M∞) 3CmD (1 − Mt/M∞)3 = 2 1 (29) dt roC0 1 − (1 − Mt/M∞)3 where Cm = drug dissolved in the membrane; C0 = initial drug concentration. This is valid when Cm <<< Ctot, that is, not more than 1% of the drug is present in the membrane. This equation assumes that the solid drug is dis- solved from surface layer ﬁrst and next layer dissolves only after the ﬁrst layer is exhausted. However, the majority of microparticulate systems are heterogeneous and drug release is complex. The equation implies that drug release is proportional to the square root of time and is simpliﬁed to Q = k t1/2 (32) 1 This is the modiﬁed Higuchi equation.
Types of Submissions Where a range of container ﬁll sizes for a drug product A bracketing design may be used for primary stability of the same strength is to be evaluated discount avana 100 mg amex erectile dysfunction needle injection video, bracketing design batches in an original application generic 50mg avana mastercard erectile dysfunction medicine with no side effects, postapproval commit- may be applicable if the material and composition of the ment batches buy avana with a visa erectile dysfunction jacksonville, annual batches, or batches intended to sup- container and the type of closure are the same throughout port supplemental changes. Such justiﬁcation should demonstrate that the batches, commitment batches, or production batches. Bracketing protocols to be applied to postap- in the same container and closure (with identical material proval commitment batches and annual batches, if pro- and size) is to be tested, bracketing design may be appli- posed, will be approved as part of the original application. If the weights of a common granulation, or a capsule range made new bracketing design is used to generate stability data to by ﬁlling different plug ﬁll weights of the same compo- support two different chemistry, manufacturing, or controls sition into different-size capsule shells. The phrase “very changes, the two proposed changes could be combined into closely related formulation” means a range of strengths one Prior Approval Supplement even though the latter may with a similar, but not identical, basic composition such otherwise qualify for a Changes Being Effected Supplement that the ratio of active ingredient to excipients remains or annual report under 314. In addition, ies, and subsequently submit the data to support the pro- data variability and product stability, as demonstrated posed change through the appropriate ﬁling mechanism. Physician Matrixing design is applicable to most types of drug prod- samples or bulk pharmacy packs intended to be repack- ucts, including immediate- and modiﬁed-release oral sol- aged should be excluded from the bracketing protocol for ids, liquids, semisolids, and injectables. Where a large number ery systems may not be amenable to, or may need addi- (for example, four or more) of sizes or strengths is tional justiﬁcation for, matrixing design. Factors diates or three batches of the middle size or strength in the bracketing design is recommended. Where the ultimate Some of the factors that can be matrixed include batches, commercial sizes or strengths differ from those bracketed strengths with identical formulation, container sizes, ﬁll in the original application, a commitment should be made sizes, and intermediate time points. With justiﬁcation, to place the ﬁrst production batches of the appropriate additional factors that can be matrixed include strengths extremes on the stability study postapproval. Such differ- with closely related formulation, container and closure ences should, however, be justiﬁed. Where additional jus- suppliers, container and closure systems, orientations of tiﬁcation for the bracketing design is needed in the original container during storage, drug substance manufacturing application, one or more of the ﬁrst production batches of sites, and drug product manufacturing sites. Data evaluation including open-dish experiments) and to be so stable that the protective nature of the container and closure system The stability data obtained under a bracketing protocol made little or no difference in the product stability should be subjected to the same type of statistical analysis (through supportive data). The same principle and pro- onstrated, if appropriate, that there is no difference in the cedure on poolability should be applied (i. If the statistical assess- ensure that the matrixing protocol would lead to a suc- ments of the extremes are found to be dissimilar, the cessful prediction of the expiration dating period when intermediate sizes or strengths should be considered to be two otherwise different container and closure systems are no more stable than the least stable extreme. General excipients or different active and excipient ratios), and The use of reduced stability testing, such as a matrixing storage conditions. Data Variability and Product Stability gram where multiple factors involved in the product are being evaluated. This section provides further guid- batches depends on the product stability and data variabil- ance on when it is appropriate to use matrixing and how ity demonstrated through clinical or developmental batches. Applicability It is assumed that there is very little variability in the The types of drug products and the types of submissions analytical methods used in the testing of stability samples. The factors that can be indicate that the product exhibits excellent stability with 48 Handbook of Pharmaceutical Manufacturing Formulations: Semisolid Products very small variability. The phrase ate stability with moderate variability in the supportive “substantial amount of supportive data” means that a suf- data, matrixing design is applicable with additional justi- ﬁcient length of stability data are available on a consider- ﬁcation. Conversely, if supportive data indicate poor prod- able number of clinical or development batches, primary uct stability with large variability, matrixing design is not stability batches, or production batches to justify the use applicable. Similarly, whether or not matrixing design can of matrixing design on primary stability batches, commit- be applied to postapproval commitment batches or sup- ment batches, or annual batches and batches for postap- plemental changes will depend on the cumulative stability proval changes. The formulations used in a matrixing data on developmental batches, primary batches, or pro- design should be identical or very closely related, and the duction batches, as appropriate. General study would be the same for a given factor or across For original applications, a matrixing design should different factors should be provided if available. Data Evaluation months, that is, at least three time points including the initial and 12-month time points. This approach is espe- The stability data obtained under a matrixing protocol cially important if the original application contains less should be subjected to the same type of statistical analysis than full long-term data at the time of submission. The same principle and procedure on attributes, different matrixing designs for different poolability (i. The only exception is that, if necessary, the drug product (two of which should be at least pilot it is acceptable to revert back to full stability testing during scale); reference is made to the drug substance and drug the study. Size of Matrixing Design batches should be made, this section provides recommen- The appropriate size of a matrix is generally related to the dations on site-speciﬁc stability data: the number and size number of combinations of factors and the amount of of drug substance and drug product stability batches made supportive data available. The size of a matrixing design at the intended manufacturing-scale production sites, and is expressed as a fraction of the total number of samples the length of stability data on these batches, for an original to be tested in the corresponding full stability protocol. Applicants are For a product available in three batches, three strengths, advised to consult with the respective chemistry review and three container or ﬁll sizes, the number of combina- team when questions arise. The larger the number of In principle, primary stability batches should be made at combinations of factors to be tested and the greater the the intended commercial site. If the primary stability amount of available supportive data, the smaller the size batches are not made at the intended commercial site, Stability Testing of Drug Substances and Drug Products 49 stability data from the drug substance product batches batches are made is located at the intended commercial manufactured at that site (i. If at the time ommendations are met (provided the processes and equip- of application submission there are 12 months of long- ment are the same) and no additional data will be needed. In addition, these site-speciﬁc batches may recommendations above would be applicable to each site. If the primary stability batch or batches are not primary stability data from another site, should be pro- made at the intended commercial site, stability data should vided at the time of application submission. Three site-speciﬁc batches are needed for a on the same campus as the intended commercial facility), complex dosage form to provide an independent and sta- the site-speciﬁc stability recommendations are met and no tistically meaningful stability proﬁle for the product made additional data will be needed. One site-speciﬁc batch may be sufﬁcient to made to place the ﬁrst three production batches and annual verify the stability proﬁle of a simple dosage form. Other factors, such as lack of experience at the new For complex dosage forms as described in the previous site in a particular dosage form or difference in the envi- section, a reduced number of site-speciﬁc batches may be ronmental conditions between the sites, can potentially justiﬁed if accelerated and long-term data are available at affect the quality or stability of a drug product. Therefore, the time of application submission on batches made at a one site-speciﬁc batch may not be sufﬁcient in these cases. General statistical analysis for the establishment of a retest period or expiration dating period. Q1B does not speciﬁcally cesses and equipment of the same design and operating address other photostability studies that may be needed to principles. If different processes or equipment are used, support, for example, the photostability of a product under more site-speciﬁc batches or longer duration of data are in-use conditions or the photostability of analytical sam- recommended. For example, if a product has been The extent of drug product testing should be established determined to photodegrade on direct exposure but is ade- by assessing whether acceptable change has occurred quately protected by packaging, an in-use study may be at the end of the light exposure testing. Light Sources Under some circumstances, photostability studies should be repeated if certain postapproval or supplemental changes, The light sources described below may be used for pho- such as changes in formulation or packaging, are made to tostability testing. The applicant should either maintain an the product or if a new dosage form is proposed. Whether appropriate control of temperature to minimize the effect these studies should be repeated depends on the photosta- of localized temperature changes or include a dark control bility characteristics determined at the time of initial ﬁling in the same environment unless otherwise justiﬁed.
Important links of the pathogenesis of this experimental model is the development of rhabdomyolysis discount 100mg avana otc erectile dysfunction pump hcpc, myoglobinuria with toxic both glomerular and tubular kidney apparatus discount avana 100mg line impotence kidney. Reamberin experimental group was administered 14 days intragastrically at a dose of 5 ml cheap 100 mg avana erectile dysfunction treatment scams. The findings of research in the control group show a decrease in serum protein level in 1. Application of Reamberin on a background of pathology significantly reduces the level of protein in the urine by 1. Reference drug Hofitol also normalized protein indicators, but without reaching the values of the investigated drug in 1. Thus, in the experimental data there is a clear positive dynamics of Reamberin complex influence on the serum and urine protein levels in experimental acute renal injury. These values allow to further explore of nephroprotective, antihypoxic properties. The basis of the secondary prevention is the use medications of long-acting penicillin. In accordance with international recommendations, benzathine benzylpenicillin-G is assigned by deep intramuscular injection once every 4 weeks (in some cases, once every 3 weeks). Children weighing 20-30 kg injected a dose of 600 units, and for all other age patient groups injected dose of 1200000 units. If the patient has allergy to penicillin, macrolides secondary prevention is carried out in cycles of 10 days each month Children who have had rheumatic fever without carditis, secondary prevention is carried out for 5 years or until the age of 21 years old. This inflammation leads to a violation of the secretory, motor, and often the endocrine functions of the stomach and duodenum. Prescribe colloidal bismuth subcitrate in a dose of 4-8 mg/kg per day in combination with amoxicillin at 25 mg/kg and nifuratel 15 mg/kg for 7 days. In the presence of an allergy to penicillin is used in the scheme clarithromycin therapy at a dose of 7. Blockers H2-histamine receptors are used in the schema therapy for children up to 12 years. Ranitidine is prescribed for 75-150 mg at twice a day for 20 minutes before eating or for famotidine 10-20 mg twice a day regardless of the meal. The drug is administered for 7-10 days and then the dose is reduced by 2 times and the treatment continues for 2-3 weeks. In children over 12 years prescribe triple therapy with the aim of eradication of Н. Four- component therapy includes nifuratel, colloidal bismuth subcitrate in combination with amoxycillin or clarithromycin. Omeprazole appoint 10-20 mg (pantoprazole 20-40 mg per day) once a day in the morning before eating for 7-10 days. Four- component therapy is indicated for the ineffectiveness three- component therapy of first-line therapy. The main cause of death, even working age is coronary heart disease due to the development cardiosclerosis. Atherosclerosis is a disease characterized by lesions of artery walls due to the formation of atherosclerotic plaques that have varying degrees of narrowing the lumen, leading to acute or chronic reduction of blood flow to vital authorities. For pharmacotherapy of atherosclerosis use following groups of drugs: statins, fibrates, bile acid sequestrants and other lipid- lowering agents. Of the group of statins are recommend following medication: lovastatin, pravastatin, simvastatin, atorvastatin, rosuvastatin. In addition, cholesterol- lowering statins are used in combination with other lipid-lowering agents: inedzhi (a combination of 20 mg of simvastatin and 10 mg of ezetimibe), and asia-ator (a combination of 10 mg of atorvastatin and 10 mgezetimibu). Quite often, the choice is between atorvastatin and rosuvastatin – modern synthetic statins, has a marked effect lipid-lowering effect. A number of studies have been conduct directly comparing the original atorvastatin and rosuvastatin. The aim of our study was to examine the results of a multicenter study compared the effectiveness of atorvastatin and rosuvastatin. Rosuvastatin has some advantage over atorvastatin in lowering total cholesterol and low-density lipoprotein cholesterol. It has been proved that long-term use rosuvastatin 40mg reduces the diameter of the atherosclerotic plaque in the vessel. Rosuvastatin had significant advantages over atorvastatin in influencing the level of inflammatory markers, as well as the progression of atherosclerosis. Atorvastatin has the largest list of indications for use for both primary and secondary prevention of cardiovascular disease. Rosuvastatin has registered indications for use - secondary prevention of cardiovascular disease. Having conducted a comparative analysis of the effectiveness of atorvastatin and rosuvastatin in the pharmacotherapy of atherosclerosis, we can conclude that both drugs are approve for use and do not have clear benefits to each other. The study of the current standards of care for patients with acute respiratory viral infections. We analyzed the articles, adapted clinical guidelines based on evidence, unified clinical protocols of emergency medical care for acute respiratory infections, including influenza. For each type of virus is the most difficult lesions characteristic of a particular department of the upper respiratory tract with the development of characteristic symptoms. Etiotropic antiviral pharmacotherapy was conduct with influenza (A and B) drugs from the group neuraminidase (oseltamivir, zanamivir). Apply the following drugs: antipyretic agents (ibuprofen, acetominiphen), antihistamines for systemic use (chloropyramine, clemastine, loratadine, dezloratadine, cetirizine), decongestants and other drugs for topical application in the case of diseases of the nose (oxymetazoline, xilometazoline, nafazoline, tramazoline, tetryzoline), antiseptics used for treatment of throat (ambazone, chlorhexidine), expectorants (guaifenesin, marshmallow root, leaf ivy), mucolytic drugs (acetylcysteine, bromhexinum, ambroxol, carbocisteine), antitussive agents (glaucine hydrobromide, okseladyn). A specific vaccine prophylaxis was carry out under the threat of epidemic (pandemic) Influenza. In 2015-2016 years in Ukraine registered the following vaccines: Vaxigrip, Influvak. Opioids – a substance derived from the opium poppy, and their synthetic analogs having similar effects. Opioids have the ability to cause drug dependence and are characterized by a strong desire to use them, they also cause tachyphylaxis, which sooner or later leads to poisoning and overdose. The aim of our study was to investigate modern rational pharmacotherapy for opiate poisoning. We was study the adapted clinical guidelines based on evidence, articles, unified clinical protocols of emergency medical care and pharmacotherapy for poisoning opiates. The main symptoms of acute intoxication by opiates are dizziness, tinnitus, dry mouth, nausea, sometimes vomiting. The skin of the face and torso hyperemic or pale, sometimes puffiness of the face, itching and rash. The body temperature is reduce, skin feels wet and cold, cold extremities is observe. Pharmacotherapy of opioid addicts consists of three main phases: detoxification (mild withdrawal syndrome); somatoneurological correction of mental disorders and primary preventive treatment; supporting preventive treatment. For the relief of withdrawal symptoms using integrated circuit with psychopharmacological agents, wegetotropic drugs, muscle relaxants, painkillers, treat with prolonged medicated sleep (with the use of anesthesia: thiopental sodium, sodium hydroxybutyrate); replacement therapy with the use of narcotic analgesics and their gradual cancellation (methadone, buprenorphine programs, the legalization of soft drugs and delivery of treated persons drugs addiction), rapid opioid detoxification. The main objectives of the second phase of pharmacotherapy are correction somatovegetativnyh postabstinent violations in the form of asthenic syndrome, vegetative and psychopathological disorders (neuroleptics: haloperidol, periciazine, amitriptyline, thioridazine hydrochloride; antiepileptic: karbmazepin, levomepromazine, analgesics: flupirtine maleate; antispasmodics: drotaverinum; alpha-blockers: pirroxan).
A combinaton of a thiazide and a loop diuretc may be required to treat refractory oedema generic avana 50 mg on-line impotence treatments natural. The combinaton ofen produces a synergistc efect on solute and water excreton 200mg avana mastercard smoking erectile dysfunction statistics, which relieves symptoms in the diuretc-resistant heart failure patent buy 50mg avana with visa erectile dysfunction gnc products. However, the combinaton may produce excessive intravascular volume depleton and electrolyte disturbances including potentally life-threatening hypokalaemia. Digoxin, a cardiac glycoside, increases the strength of cardiac muscle contractons and increases cardiac output. In mild heart failure, digoxin inhibits the sympathetc nervous system and produces arterial vasodilaton. It produces symptomatc improvement, increases exercise tolerance and reduces hospi- talizaton, but it does not reduce mortality. Isosorbide dinitrate produces mainly venous dilataton, which reduces lef ventricular preload, leading to a reducton in pulmonary congeston and dysp- noea. Hydralazine produces mainly arterial vasodilaton, which reduces lef ventricular aferload and increases stroke volume and cardiac output. Dopamine, an inotropic sympathomimetc, may be given for short periods in the treatment of severe heart failure. Dosage is critcal; at low doses it stmulates myocardial contractlity and increases cardiac output, however, higher doses (more than 5 µg/kg per min) cause vasoconstricton, with a wors- ening of heart failure. Adverse Efects Tachycardia and marked increase in systolic blood pressure indicate overdosage; phlebits; rarely, thrombocytopenia. Dopamine* Pregnancy Category-C Schedule H Indicatons Cardiogenic shock in myocardial infarcton or cardiac surgery; acute heart failure. Dose Intravenous infusion Adult- Cardiogenic shock: into large vein, initally 2 to 5 µg/kg/min; gradually increased by 5 to 10 µg/kg/min according to blood pressure, cardiac output and urine output; seriously ill patents up to 20 to 50 µg/kg/ min. By intravenous route initally 1 to 5 µg/ kg/min can be increased gradually to 5 to 10 µg/kg/min. Contraindicatons Hypersensitvity; tachyarrhythmias, ven- tricular fbrillaton, ischaemic heart disease; pheochromocytoma; hyperthyroidism. Precautons Correct hypovolaemia before and maintain blood volume during treatment; correct hypoxia; hypercapnia and metabolic acidosis before or at same tme as startng treatment; low dose in shock due to myocardial infarcton; history of peripheral vascular disease (increased risk of ischaemia of extremites); elderly; interactons (Appendix 6c); history of atherosclerosis; Raynaud’s disease; diabetc endocardits; dispropotonate increase in diastolic pressure; pregnancy (Appendix 7c); lactaton; paediatrics. Adverse Efects Nausea and vomitng; peripheral vasoconstricton; hypotension with dizziness; faintng; fushing; tachycardia; ectopic beats; palpitatons; anginal pain; headache; dyspnoea; hypertension partcularly in overdosage. Slow intravenous injecton Adult- Acute pulmonary oedema: 20 to 50 mg, if necessary increase by 20 mg step-by- step every 2 h; if efectve single dose is more than 50 mg, at a rate not exceeding 4 mg/ min. Slow intravenous infusion Adult- Oliguria (glomerular fltraton rate less than 20 ml/min): at a rate not exceeding 4 mg/min, initally 250 mg over 1 h. If urine output not satsfactory during the h afer frst dose, infuse 500 mg over 2 h then; if no satsfactory response is there in an h afer second dose, infuse 1g over 4 h. Contraindicatons Renal failure with anuria; precomatose states associated with liver cirrhosis; severe sodium and water depleton; hypersensitvity to sulphonamides and furosemide; hypokalaemia; addison’s disease; lactaton. Adverse Efects Hypokalaemia; hypomagnesaemia; hyponat- raemia; hypochloraemic alkalosis (for symp- toms of fuid and electrolyte imbalance; see introductory notes); increased calcium excreton; hypovolaemia; hyperglycaemia (but less ofen than with thiazide diuret- ics); temporary increase in plasma cho- lesterol and triglyceride concentraton; less commonly hyperuricaemia and gout; rarely, rash; photosensitvity; bone marrow depression (withdraw treatment); pancreat- ts (with large parenteral doses); tnnitus and deafness (with rapid administraton of large parenteral doses and in renal impairment; deafness may be permanent if other ototoxic drugs taken); gastrointestnal upset; malaise; blood dyscrasias; vertgo; orthostatc hypo- tension; jaundice; tnnitus; renal calcifcaton in premature infants. Various classes of drugs used as lipid lowering drugs are- H mg-CoA reductase inhibitors They are the most efcacious and tolerable drugs like simv- astatn, pravastatn, atorvastatn etc. They are primarily indi- cated in secondary preventon of myocardial infarcton and stroke in patents who have symptomatc atherosclerotc disease following acute myocardial infarcton or stroke and in primary preventon of arterial disease in patents who are at high risk because of elevated serum cholesterol concentra- ton. Common adverse efects include mild gastrointestnal disturbances, rhabdomyolysis etc. Fibric acid derivatves This class of drugs including fenofbrate, gemfbrozil etc are indicated in patents with mixed dyslipidemia (i. Bile acid sequestrants Drugs like cholestyramine, colestpol though are not clinically popular because of interference with absorpton of many drugs like digoxin, warfarin etc and poor patent acceptability, but can be indicated in heterozygous familiar hypercholeste- rolemia. Adverse efects include fushing, palpitatons and gastrointestnal tract disturbances. Contraindicatons Hypersensitvity; actve liver diseases or unexplained persistent elevaton of serum transaminase; pregnancy (Appendix 7c), lactaton. Precautons Patents who consume substantal quanttes of alcohol and have a history of liver diseases, Children below 10 years, premenarcheal females; interactons (Appendix 6a, 6c). Adverse Efects Myopathy is the serious adverse efect; headache; infrequent elevaton of creatnine phosphokinase; rhabdomyolysis; insomnia; dizziness; abdominal pain, constpaton, diarrhoea, dyspepsia, fatulence and nausea. Ezetmibe Pregnancy Category-C Indicatons Hypercholesterolemia, hyperlipidaemias, homozygous familial sitosterolaemia. Contraindicatons Hypersensitvity, children below 10 years, pregnancy (Appendix 7c), interactons (Appendix 6c, 6d), lactaton, moderate to severe liver disease or unexplained serum transaminase elevaton, acute pancreatts. Precautons Renal or mild hepatc impairment, immediately discontnue ezetmibe and any H mg-CoA reductase inhibitor or fbrates if myopathy is diagnosed. Storage Store protected from light and moisture at a temperature not exceeding 30⁰C Fenofbrate Pregnancy Category-C Schedule H Indicatons Hypercholesterolemia, hypertriglyceridemia. Dose Hyperlipidemia: Adult- Inital dose 67 mg 2-4 tmes a day (micronized) or 200 mg/day in divided doses (non-micronized). Contraindicatons Hypersensitvity, severe renal and hepatc impairment, preexistng gall bladder disease, primary biliary cirrhosis, pregnancy (Appendix 7c), lactaton. Nicotnic acid Pregnancy Category-C Schedule H Indicatons High risk hyperlipidaemia, nicotnic acid defciency, peripheral vascular disease. Hyperlipidaemia: Adult- 1-2 g, two to three tmes daily, maximum dose- 6 g per day; (As extended release tablets max. Peripheral vascular disease: Adult- 100- 150 mg, three to fve tmes daily; (Extended release preparaton-) 300-400 mg 12 hourly. Contraindicatons Hypersensitvity, liver disease, severe hypotension, diabetes, arterial bleeding. Precautons Gout, hepatc dysfuncton, children, pregnancy (Appendix 7c), lactaton, myasthenia gravis, interactons (Appendix 6a and 6c). Adverse Efects Headache, diarrhoea, vomitng, faintng, peptc ulcer, hyperuricaemia, gout, toxic amblyopia, fushing, hyperpigmentaton, dry skin, muscle pain, jaundice, pruritus, atrial fbrillaton. Flushing can be blocked by administering 300 mg of aspirin half an hour before taking niacin, or by taking one tablet of ibuprofen per day. In all skin infectons, an important part of treatment is cleansing and thorough drying. Light localized infectons can ofen be treated efectvely with an antseptc soluton such as chlo- rhexidine. Superfcial crusts should be gently washed with soap and water or a weak soluton of aluminium acetate or a 0. Infected burns should be treated with silver sulfadiazine, which is bactericidal against both Gram-positve and Gram-negatve organisms.
Dextran nanoparticle–vitamin B12 combination showed a release proﬁle that was suitable for oral delivery systems of insulin purchase avana 200 mg line top rated erectile dysfunction pills. The associated conditions are inﬂammatory diseases of skin and gums order avana 200mg online constipation causes erectile dysfunction, diabetic retinopathy (eyes) cheap 100mg avana mastercard erectile dysfunction medication with no side effects, diabetic neu- ropathy (nervous system), heart diseases, kidney diseases, delayed wound healing, and many more. Nanoparticulate systems have also been tested for the treatment of these associated conditions. Nanoparticle-based ocular drug delivery systems have been already described in the past decade (39,40). The scientiﬁc com- munity is working toward utilizing nanoparticle-based drug delivery systems for the treatment of diabetes-associated complications. These research studies are being conducted to under- stand how matter behaves at the nanoscale level. Factors and conditions governing the behavior of macrosystems do not really apply to the nanosystems. The major limitations and technological hurdles faced by nanotechnology and its applica- tions in the ﬁeld of drug delivery should be addressed (44,45). Scientiﬁc commu- nity has not yet understood completely how the human body would react to these nanoparticles and nanosystems, which are acting as drug carriers. Friction and clumping of the nanoparticles into a larger structure is inevitable, which may affect their func- tion as a drug delivery system. Due to their minute size, these drug carriers can be cleared away from the body by the body’s excretory pathways. When these are not excreted, larger nanoparticles can accumulate in vital organs, causing toxicity lead- ing to organ failure. Recent study in mice revealed that tissue distribution of gold nanoparticles is size dependent, with the smallest nanoparticles (15–50 nm) show- ing the most widespread organ distribution including blood, liver, lung, spleen, kidney, brain, heart, and stomach (46). Liposomes have certain drawbacks, such as being captured by the human body’s defense system. The drug-loading capacity of liposomes is being tested by researchers and still remains inconclusive. All previ- ous studies resulted in posttreatment accumulation of the nanoparticles in skin and eyes. Once the nanoparticles are administered into the human body, they should be controlled by an external control, preventing them from causing adverse effects. These drug deliv- ery technologies are in various stages of research and development. It is expected that these limitations can be overcome and the discoveries to come into practical use within the next 5 to 10 years. Report of the Committee on the classiﬁcation and diagnostic criteria of diabetes mellitus. Formulation of insulin-loaded polymeric nanoparti- cles using response surface methodology. Glucose-sensitive membranes containing glucose oxidase: Activity, swelling, and permeability studies. Control of insulin permeation through a polymer membrane with responsive function for glucose. Novel oral microspheres of insulin with protease inhibitor protecting from enzymatic degradation. Pelleted bioadhesive polymeric nanopar- ticles for buccal delivery of insulin: Preparation and characterization. Preparation of stable insulin-loaded nanospheres of poly(ethylene glycol) macromers and N-isopropyl acrylamide. Bioadhesive polysaccharide in protein delivery system: Chi- tosan nanoparticles improve the intestinal absorption of insulin in vivo. Preparation and characterization of nanoparticles shelled with chitosan for oral insulin delivery. Development and characterization of new insulin containing polysaccharide nanoparticles. Cyclodextrin-insulin complex encapsulated polymethacrylic acid based nanoparticles for oral insulin delivery. Oral and subcutaneous absorption of insulin poly(isobutylcyanoacrylate) nanoparticles. Vesicles from pluronic/poly(lactic acid) block copolymers as new carriers for oral insulin delivery. Poly(dl-lactide-co-glycolide) nanoparticle-based inhalable sustained drug delivery system for experimental tuberculosis. Self-assembled carbohydrate-stabilized ceramic nanopar- ticles for the parenteral delivery of insulin. Prolonged hypoglycemic effect of insulin-loaded polybutyl- cyanoacrylate nanoparticles after pulmonary administration to normal rats. Absorption of peptides and proteins from the respiratory tract and the potential for development of locally administered vaccine. Effective insulin delivery using starch nanopar- ticles as a potential trans-nasal mucoadhesive carrier. Characterization of micromachined silicon membranes for immunoisolation and bioseparation applications. Chitosan reduced gold nanoparticles as novel carriers for transmucosal delivery of insulin. A novel vitamin B12-nanosphere con- jugate carrier system for peroral delivery of insulin. Brimonidine formulation in polyacrylic acid nanoparticles for ophthalmic delivery. Ocular drug delivery targeting the retina and reti- nal pigment epithelium using polylactide nanoparticles. Chitosan nanoparticles as a poten- tial drug delivery system for the ocular surface: Toxicity, uptake mechanism and in vivo tolerance. Superparamagnetic nanoparticles for biomed- ical applications: Possibilities and limitations of a new drug delivery system. Biodistribution of colloidal gold nanoparticles after intravenous administration: Effect of particle size. Nanosystems for Dermal and Transdermal Drug Delivery Venkata Vamsi Venuganti and Omathanu P. Perumal Department of Pharmaceutical Sciences, South Dakota State University, Brookings, South Dakota, U. However, the unique bioarchitecture of skin lim- its the transport of molecules through it (1). The skin also has appendages such as hair follicles and sweat pores, which constitute 0. The hair follicles originate from the dermis and terminate at the surface of the skin.