By U. Temmy. University of Texas Medical Branch. 2018.
The recent emergence of nanotechnology has opened up new opportunities to develop nanosystems for topical and transdermal applications cheap septilin 60caps on line. If not all septilin 60caps low price, some of these nanosystems have been speciﬁcally developed for skin applications. The nanosystems can be classiﬁed based on the properties of the carriers as shown in Figure 2. For drug delivery applications, the nanosystems generally range in size from 1 to 1000 nm. The goal of this chapter is to provide a comprehensive overview of the formulation characteristics, mechanism of skin penetration, applications, and future prospects of nanosystems for dermal and transdermal drug delivery systems. On mixing with an aqueous medium, the phosphate groups of the phospholipids orient themselves to the hydrophilic environment spontaneously forming unilamellar or multilamellar bilayer vesicles (Fig. Cholesterol is usu- ally included to improve the stability of the vesicles, impart ﬂuidity to the bilayer membrane, and prevent the leakage of vesicle contents (14). In addition, steary- lamine or diacetyl phosphate can be included to impart a net positive or negative charge respectively (15). Hydrophilic drugs are incorporated in the aqueous core, whereas lipophilic drugs are entrapped within the bilayer. In general, hydrophilic drugs have higher encapsulation efﬁciency than lipophilic drugs (14). The use of liposomes as a topical delivery carrier was ﬁrst demonstrated by Mezei and Gulasekharam (17). In comparison to topical application of a simple lotion, the liposomes delivered four to ﬁve fold higher steroid concentrations in the skin layers. Since then, there has been an exponential growth in the use of liposomes as topical delivery vehicles (15). On the other hand, the use of liposomes as trans- dermal drug delivery vehicles is debatable (18). Now it is clear that the conventional liposomes have little value for transdermal drug delivery and in fact may decrease the drug penetration (18). The organic solvent is removed under reduced pressure and lyophilized to remove any traces of solvent. The thin lipid ﬁlm is redispersed in aqueous medium and sonicated to give a uniform dispersion. Reverse-phase evaporation A water-in-oil emulsion is prepared by dissolving phospholipids in the organic phase. Ether injection method Lipid is dissolved in ether and injected into the aqueous medium at a very slow rate. Skin penetration of liposomes is inﬂuenced by their size, composition, lamellarity, and charge (15,18). The mechanism of skin pen- etration of liposomes has been attributed to the penetration-enhancing properties of phosopholipids, increased skin partitioning of drug, adsorption of liposomes onto the skin, and penetration through transappendageal pathways (15,18). The phase- transition temperature of lipids in the liposomes inﬂuences their penetration and interaction with the skin lipids (19). Lipids in the liquid state penetrate deeper than do lipids in the gel state at the skin temperature (19). Studies have shown that liposomes adsorb and fuse with the skin surface and form a favorable environment for the partitioning of lipophilic drugs (18–20). On the other hand, intact liposomes can penetrate through the appendageal pathways, fuse with the sebum, and slowly release the drug (20). As a result, lipo- somes have been used to target therapeutics to the follicles (21).
The detailed observations about the infrastructure buy cheap septilin 60 caps on line, technical personnel and other set up of the testing facility applied for instrumental order septilin 60caps mastercard, chemical and microbiological analysis of Drugs and pharmaceuticals or raw materials used in the manufacture there of on behalf of licensees for manufacture for sale of Drugs were noted and summarized in aforesaid checklist. Following observations were made by the joint inspection team during the course of inspection. Observations Conclusion & Recommendation :- On the basis aforesaid inspection checklist and summarized observations it may be concluded that M/s. In the view of above the inspecting team is of the opinion that the application furnished by the subject firm as per Form 36, for approval to carry out test on Drugs & pharmaceuticals or raw materials used in the manufacture thereof on behalf of 382 licensees for manufacture for sale of Drugs or raw material on Form-37 for following categories of Drugs by Chemical, Instrumental & Microbiological testing may be granted for the followings category of the drugs & Cosmetics: Drugs other than those specified in schedule C & C(1) excluding Homeopathic Drugs Drugs requiring the use of ultraviolet spectroscopy or chromatography Disinfectants Cosmetics b. Procedure Under the provision of Rule – 89 it is mentioned that “in the case of a drug, the composition of which is such that the drug is not generally recognized among experts qualified by scientific training and experience to evaluate the safety of drugs as safe for use, no licence in Form – 29 shall be granted unless the applicant produces a certificate from the “Licensing Authority” mentioned in Rule 21, to the effect that there would be No Objection to such license being granted”. This document made as per guidelines issued by Ministry of Health and Family Welfare for Export purpose and Rule 94 of the Drugs and Cosmetic Act, 1940. Covering Letter: - The covering letter is an important part of the application and should clearly specify the intent of the application. The list of documents that are being submitted (Index with page no‘s) as well as any other important and relevant information may be provided in the covering letter. The covering letter mentioning list of products to be exported clearly indicating name of the drug, dosage form, composition and strength pack size along with quantity and country to be exported duly signed and stamped by the authorized signatory, indicating the name & designation of the authorized signatory along with the name and address of the firm. Order from the foreign buyer either in the name of manufacturer or in the name of trader mentioning list of products to be exported clearly indicating name of the drug, dosage form, composition and strength pack size duly signed by the competent authority with specific destination point of the importing country. In case of purchase order in the name of trader further a letter from the trader in the name of manufacturer is required to be submitted along with the application b. It should be signed by the competent authority/person with a valid purchase order no. Manufacturing License: - License issued by the State Licensing Authority should be enclosed along with each application for the required location to manufacture the drug for export purpose. A copy of Performa invoice from the importing country should accompany with application for import of unapproved Active Pharmaceutical Ingredients, used in the drug formulation. A copy of Performa invoice duly signed by the competent authority should be addressed to the manufacturer mentioning the required quantity of the bulk drug. For the export of drugs which are banned in India by Central government, which coming under list of drugs prohibited for manufacture and sale through gazette notifications under section 26a of drugs & cosmetics act 1940 by the ministry of health and family welfare. A copy of registration certificate from the specific importing country along with composition and strength of the drug should accompany with the application c. While processing such applications the following conditions shall be taken into consideration: 1. The applicant shall identify the premises where the drug will be manufactured for export. The applicant should mention whether the batch to be exported has undergone Quality control testing or shall be tested at the destined site. The applicant shall make available for inspection of the appropriate authorities, on completion of the export orders, information regarding each consignment despatched, remaining stock of drug and related raw materials and intermediates in hand. The applicant shall ensure physical destruction of all un exported quantity of drugs. This should be included as a condition of manufacturing license issued to the applicant by the State licensing authority.
Ease of administration Nasal devices generic 60caps septilin mastercard, such as metered-dose nasal sprays purchase septilin 60 caps visa, are simple for the patient to use and might be expected to be more acceptable to the patient than the use of pessaries or suppositories for the intravaginal and rectal delivery routes respectively. Intestinal alternative The nasal route may become a useful alternative to the intestinal route for drug absorption in situations where use of the gastrointestinal route is unfeasible. Examples include: • patients with nausea and vomiting; 234 • patients with swallowing difficulties and/or children; • drugs that are unstable in the gastrointestinal fluids; • drugs that undergo extensive first-pass effects in the gut wall or liver. For drugs which are rapidly absorbed, mucociliary clearance is likely to be of little consequence, but for those compounds with physicochemical properties dictating slow absorption the effect of mucociliary clearance is likely to be profound. Mucus barrier Drug diffusion may be limited by the physical barrier of the mucus layer and the binding of drugs to mucins. Limited to potent molecules For drugs of a high molecular weight (which are thus poorly absorbed), the route is limited only to potent drug molecules; typically those with effective plasma concentrations in the ng mL−1 (or lower) range. Lack of reproducibility The major problem associated with intranasal delivery is the question of whether it can provide reliable absorption. Diseases such as the common cold and hayfever are recognized to alter the condition of the nose, either increasing or decreasing mucociliary clearance, or altering the permeability of the absorbing mucosa. The frequency with which these diseases occur means that patients requiring chronic drug therapy will undergo periods when drug absorption might be expected to be higher or lower than “normal”. Adverse reactions Locally irritating or sensitizing drugs must be used with caution in this route. This contrasts with, for example, the buccal epithelium which is much more robust and less prone to irritation. The fragility of the tissue also means that this route is particularly sensitive to the adverse effects of penetration enhancers. Damage to the epithelium could result in compromised mucocilary clearance which is associated with respiratory disease. Some intranasally delivered drugs showing systemic absorption are given in Table 9. They are also available as metered-dose devices, which would be expected to give more reproducible dosing, as a mechanical actuation delivers a pre-determined volume to the patient. Thus the dose of drug received by the patient will be dependent on the concentration of drug in the formulation. Commercial examples of metered-dose sprays include Syntaris, Beconase and Rhinocort which deliver flunisolide, beclomethasone and budesonide respectively. As discussed above, nasal sprays tend to deposit at their impaction site, in the anterior, unciliated regions of the nasal cavity, where airflow associated with inspiration is high and mucociliary clearance is slow or erratic. Thus a drug moiety depositing in this region is cleared slowly and is transported over a large area en route to the pharynx. As described above, nasal drops, if administered correctly, deposit drug throughout the nasal cavity (Figure 9. However this also means that: • some drug is inevitably deposited on ciliated regions of the mucosa and is therefore immediately available for clearance; • a proportion of the dose actually deposits at the nasopharynx where it may be immediately swallowed and is therefore not available for nasal absorption. To ensure a complete coating of the nasal mucosa from the atrium to the nasopharynx, the method depicted in Figure 9. Since this is either unknown or inconvenient to most patients, variable drug absorption is likely to result, which would be unacceptable for drugs with a narrow therapeutic window. In this second slower phase, clearance of the drops is much faster than clearance of the spray, probably because most of the spray deposits on non-ciliated regions.
Hyperglycaemia and Diabetes Mellitus Hyperglycaemia cheap septilin 60caps on-line, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death generic septilin 60caps without a prescription, has been reported in patients treated with atypical antipsychotics including olanzapine. Tardive Dyskinesia A syndrome of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with antipsychotic drugs. Olanzapine has not been evaluated or used to any appreciable extent in patients with a recent history of myocardial infarction or unstable heart disease. Because of the risk of orthostatic hypotension with olanzapine, caution should be observed in cardiac patients During premarketing testing, seizures occurred in 0. Because this enzyme system is regarded as the acid (proton) pump within the gastric mucosa, omeprazole has been characterised as a gastric acid-pump inhibitor, in that it blocks the final step of acid production. Inter-patient variability requires that each patient is carefully titrated to the appropriate dose. A study of OxyContin in patients with hepatic impairment indicates greater plasma concentrations than those with normal function. The initiation of therapy at 1/3 to 1/2 the usual doses and careful dose titration is warranted in such patients. OxyContin and other morphine-like opioids have been shown to decrease bowel motility. In this case, use the diluted solution within the hour following its preparation (infusion time included). This monitoring at the end of the perfusion applies particularly for central route infusion, in order to avoid air embolism. It is recommended that for the administration of Perfalgan 10mg/mL solution for infusion a syringe or giving set with a diameter equal to or below 0. In addition, it is recommended that the bung is pierced at the location specifically designed for needle introduction (where the thickness of the bung is the lowest). If these recommendations are not adhered to the likelihood of bung fragmentation or the bung being forced into the vial is increased. The precise mechanism of the analgesic and antipyretic properties of paracetamol has yet to be established; it may involve central and peripheral actions. Hyponatraemia Cases of hyponatraemia (some with serum sodium lower than 110 mmol/L) have been reported. Pulmonary events, including inflammatory processes of varying histopathology and/or fibrosis, have been reported rarely. Published case reports have documented the occurrence of bleeding episodes in patients treated with psychotropic drugs that interfere with serotonin reuptake. Subsequent epidemiological studies, both of the case-control and cohort design, have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. Patients on stable doses of phenytoin and carbamazepine have developed elevated plasma anticonvulsant concentrations and clinical anticonvulsant toxicity following initiation of concomitant fluoxetine treatment. Respiratory depression occurs most frequently in the elderly and debilitated patients as well as in those suffering from conditions accompanied by hypoxia or hypercapnia when even moderate therapeutic doses may dangerously decrease pulmonary ventilation. Pethidine should be used with extreme caution in patients with chronic obstructive pulmonary disease or cor pulmonale, and in patients having a substantially decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression. In such patients, even usual therapeutic doses of morphine may decrease respiratory drive while simultaneously increasing airway resistance to the point of apnoea. Hypotensive Effect Morphine sulphate controlled-release tablets, like all opioid analgesics, may cause severe hypotension in an individual whose ability to maintain his blood pressure has already been compromised by a depleted blood volume, or a concurrent administration of drugs that lower blood pressure. Convulsions Pethidine may aggravate pre-existing convulsions in patients with convulsive disorders. If dosage is escalated substantially above recommended levels because of tolerance development, convulsions may occur in individuals without a history of convulsive disorders.
They discussed the rationale for selecting optimal strategies of liposomal drug formulations with respect to drug encapsula- tion cheap septilin 60 caps free shipping, retention generic 60caps septilin free shipping, and release, and how these strategies can be applied to maximize the therapeutic beneﬁt in vivo. An interesting review about the application of nanopar- ticulate drug delivery systems in nasal delivery is reported by Illum (90). Gene therapy is considered to be a promising therapeutic strategy to combat root causes of genetic or acquired diseases rather than just treating the symptoms (97). There is a need for nontoxic and efﬁcient gene delivery vectors; an interest- ing review by Mozafari and Omri discusses important aspects of divalent cations in nanolipoplex gene delivery (91). They reviewed the role of divalent cations in nucleic acid delivery, particularly with respect to the potential improvement of transfection efﬁciency of nanolipoplexes. The size and surface chemistry of mesoporous silicon-based drug delivery systems can be useful in delivering many drugs, including protein and peptide drugs. The review covered the fabrication and chemical modiﬁcation of mesoporous silicon-based drug delivery systems for biomedical applications and also discussed the potential advantages of these delivery systems. The review covered potential applications of dendrimers as polymeric carri- ers for intravenous, oral, transdermal, and ocular delivery systems. They discussed the dendrimer–drug interactions and mechanisms, encapsulation, electrostatic Recent Developments in Nanoparticulate Drug Delivery Systems 11 interactions, and covalent conjugation of drug and dendrimer molecules. The appli- cation of nanotechnology to drug delivery is widely expected to create novel ther- apeutics, capable of changing the landscape of pharmaceutical and biotechnol- ogy industries. Various nanotechnology platforms are being investigated, either in development or in clinical stages, and many areas of interest where there will be effective and safer targeted therapeutics for a myriad of clinical applications. Multifunctional nanocarriers for mammo- graphic quantiﬁcation of tumor dosing and prognosis of breast cancer therapy. Dendrimer-modiﬁed magnetic nanoparticles enhance efﬁ- ciency of gene delivery system. Immunogenecity of bioactive magnetic nanoparticles: Nat- ural and acquired antibodies. Synthesis and characterization of chitosan- g-ploy(ethylene glycol)-folate as anon viral carrier for tumor targeted gene delivery. Amine containing core shell nanoparticles as potential drug carriers for intracellular delivery. Developments on drug delivery systems for the treatment of mycobacterial infections. Facile biosynthesis, separation and conjugation of gold nanoparticles to doxorubicin. Mesoporous silicon particles as a multistage delivery system for imaging and therapeutic applications. A nanoparticulate drug delivery system for rivastigmine: Physicochemical and in vitro biological characterization. Recent developments in nanoparticle based drug delivery and tar- geting systems with emphasis on protein based nanoparticles. Characterization of the morphology and thermal properties of Zein Prolamine nanostructures obtained by electrospinning. Formation of silk ﬁbroin nanoparticles in water miscible organic solvent and their characterization. Nanoparticulate drug delivery systems for the non-invasive chemotherapy of brain tumors. Self assembled drug delivery systems; part I: In vitro in vivo studies of the self assembled nanoparticulates of cholesteryl acyl didanosine.
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