Investigation of transdermal permeation of atorvastatinloaded microemulsions (original) (raw)
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Pharmaceutical Formulation and Biochemical Evaluation of Atorvastatin Transdermal Patches
Indian Journal of Pharmaceutical Education and Research, 2018
Atorvastatin is a lipid lowering agent and widely used to treat hypercholestermia. However following oral administration, the bioavailability of the drug is only 12% due to extensive first pass metabolism. The aim of the current research was to formulate ATO-transdermal patches utilizing various polymers combinations. Hydroxypropyl methylcellulose with either eudragit RS100 or Polyvinylpyrrolidone were mixed in different ratios, in presence of polyethylene glycol 400 as plasticizer. The patches were prepared by solvent evaporation method. Physicomechanical parameters such as, drug content, patch thickness, tensile strength, moisture loss and moisture gained were evaluated. Additionally drug excipient compatibility was assessed by FTIR and DSC. In vitro drug release was measured in phosphate buffer pH 7.4 at 37 °C. Finally, biochemical evaluation of the best formulae was evaluated on hyperlipidemic-induced rats. The results indicated that, Hydroxypropyl methylcellulose: Polyvinylpyrrolidone in a ratio of 3:1 showed the most appropriate physicomechanical characters with confirmed physical and chemical drug-polymer compatibility. In addition, the in-vitro experiment showed enhanced atorvastatin release over 24 hr. The pharmacological evaluation of F2 formula indicated a significant hypolibedimic effect compared to orally administered atorvastatin. The results revealed that, atorvastatin transdermal patch could be considered as promising drug delivery system for hyperlipidemic patients.
Development of Dispersible Self-microemulsifying Tablet of Atorvastatin
Pharmaceutical Methods, 2015
Aim: The aim of this study was to develop dispersible self-microemulsifying (SMEDDS) tablet of atorvastatin for promoting its solubility and thus its oral bioavailability. Materials and Methods: The liquid SMEDDS were prepared by water titration method using oil, surfactant and co-surfactant and converted into solid-SMEDDS (S-SMEDDS) by adsorption on solid carriers (Neusilin US2). The S-SMEDDS were blended with sodium starch glycolate (disintegrant) and tablet excipients and compressed into tablets that were dispersible and self-microemulsifying in nature. All these formulations were assessed for various physicochemical parameters viz. weight variation, hardness, friability, disintegration test. In vitro studies of pure drug, SMEDDS, S-SMEDDS and dispersible SME-tablets were carried out. Results: Pure drug released only 29.84 ± 0.16% upto 60 minutes and all the SMEDDS formulations (i.e. SMEDDS. S-SMEDDS and dispersible SME-tablets) released 100% of drug in comparatively lesser time. Formulations containing atorvastatin, 30% oleic acid, 65% tween 80 and 5% co-surfactant came out to show the best results in in vitro studies. But, FB1 (tablet) was considered to be the best since it released 100% drug in 35 min and also has advantages over SMEDDS and S-SMEDDS in terms of stability and patient compliance. Conclusion: The study revealed the potential use of dispersible SMEDDS tablet for the oral delivery of hydrophobic drugs, such as atorvastatin.
pharmacokinetic advances: New formulations of application on the skin and oral mucosa
Currently a growing interest to improve the pharmacological therapy exists, not only by the production and the appearance of new drugs, but guaranteeing that the uses of those which already exist, become more effective. In fact, the conventional pharmaceutical formulations of different drugs present a few secondary effects due to oral administration. In order to avoid these undesired side effects, the purpose of current therapeutic is the development and research of formulations as an alternative to others routes of administration. Therefore, in spite of the undoubtedly complete parenteral absorption, the transdermal and transbuccal routes appear to be a rather attractive alternative to provide an efficient absorption. In this chapter a new technological, biopharmaceutical and pharmacokinetic approach of strategies for application on skin and buccal mucosa are reported.
FORMULATION AND EVALUATION OF TRANSDERMAL DRUG DELIVERY SYSTEM CONTAINING ANTI-INFLAMMATORY AGENT.
Aim of the present study was to develop site-specific drug delivery system of lornoxicam for the treatment of arthritis, pain etc., which has excellent activity on inhibition of Cyclooxygenase-1 and Cyclooxygenase-2 enzymes. The formulations were developed by utilizing variouspolymers such as hydroxy propyl methyl cellulose and Eudragit RL-100 by solvent casting technique by the use of plasticizer (PEG-400 & DBT). The calibration curve of lornoxicam was developed in methanol/water. Compatibility study was carried out by FT-IR and Differential scanning colorimetry. The formulations were evaluated for thickness, folding endurance, weight variation, drug content, percent moisture loss, tensile strength. In vitro drug release study was also carried out by using PBS pH 7.4 and the samples were analyzed UV-spectrophotometrically at 374 nm. FT-IR and DSC study revealed no interaction between drug and polymers. Formulations shown good uniformity of drug content, there was no any kind of effect on moisture loss test. Formulations showed thickness within the range of (0.072 to 0.119). Formulation F1, F2, F5 & F6 showed good tensile strength. By increasing the concentration of Eudragit RL-100 in the formulation tensile strength, and folding endurance increases. Formulation F6 shows the release of drug 96.74% at the end of 12 h and was considered as a best formulation. A short‐term stability study of the optimized formulation (F6) was also carried out at 400C for three months. At periodic interval 0, 30, 60, and 90 days a known quantity of sample was withdrawn and then analyzed for drug content and in vitro drug release studies, results showed a good content of uniformity and 95.23% release was observed at the end of 90 days. After a short-term stability study, there was no or very little amount of degradation was observed.
Formulation, in vitro evaluation and characterization of atorvastatin solid dispersion
Tropical Journal of Pharmaceutical Research
Purpose: To formulate a polymer-incorporated solid dispersion preparation for enhancing the dissolution and bioavailability of atorvastatin calcium trihydrate (ATV), while maintaining oral compatibility.Method: Four different methods, i.e., physical mixing (PM), fusion (F), solvent evaporation (SE) and kneading (K), as well as three different excipients i.e. croscarmellose sodium (CCS), microcrystalline cellulose (MCC) and lactose (LAC) were used to formulate various drug-carrier combinations.Results: In SE method, the rank order of magnitude of drug release was CCS > LAC > MCC, while in fusion and kneading methods, the rank order of release was MCC > CCS > LAC and MCC > CCS > LAC, respectively. Drug release of atorvastatin was maximum (103 %) in FM2 formulation. However,this formulation was non-compatible based on spectroscopic analysis. In contrast, SC2 formulations at 1:2 ratio were compatible in terms of cumulative drug release (99 %), and based on spectroscopi...
Development and Characterization of Transdermal Drug Delivery Systems for Diltiazem Hydrochloride
Drug Delivery, 2003
The objective of this study was to design and develop o/w microemulsion for transdermal delivery of poorly water soluble acyclovir by aqueous titration method. Oleic acid: castor oil (3:1), tween 80, and ethanol were selected as oily phase, surfactant and cosurfactant respectively. The Pseudoternary phase diagrams were constructed by aqueous titration method. The cosurfactant affect the shape and extant of microemulsion regions. Ethanol (cosurfactant) is expected to disorder the interfacial film gave extended microemulsion zones by destabilizing the liquid crystalline phase. Largest Microemulsion single phase region was found at S mix (2:1) than the system at other S mix . Characterization of microemulsion were done for droplet Shape and size, refractive index, pH, Viscosity, drug loading capacity. The mean droplet size of microemulsion was found below 50 nm. The maximum solubility of ACV in microemulsion system was found to be 47.4 mg/ml. The ex-vivo skin permeation studies were done using skin of Wistar albino rat by Franz diffusion cell, and microemulsion formulation MEC1 exhibited highest flux, was found to be 238.1±4.87 µg/cm 2 /hr, while flux of MEGel, aqueous solution and conventional emulsion of ACV were found to be 230.40±6.23 µg/cm 2 /hr, 2.47±0.76 µg/cm 2 /hr and 8.65 ±1.21 µg/cm 2 /hr respectively. The pharmacokinetic parameters of MEGel after topical application to the Wistar albino rat skin were significantly different from those of ACV in aqueous solution (PD) and conventional emulsion (CE). It can be concluded that microemulsion of ACV prepared with Oleic acid: castor oil (3:1) as oily phase, tween80 as surfactant, and ethanol as cosurfactant can be used as transdermal drug carrier for this and other poorly water soluble drug.
Molecules, 2015
The objective of this work was to design and characterize liquid and solid self-emulsifying drug delivery systems (SEDDS) for poorly soluble atorvastatin. To optimize the composition of liquid atorvastatin-SEDDS, solubility tests, pseudoternary phase diagrams, emulsification studies and other in vitro examinations (thermodynamic stability, droplet size and zeta potential analysis) were performed. Due to the disadvantages of liquid SEDDS (few choices for dosage forms, low stability and portability during the manufacturing process), attempts were also made to obtain solid SEDDS. Solid SEDDS were successfully obtained using the spray drying technique from two optimized liquid formulations, CF3 and OF2. Despite liquid SEDDS formulation, CF3 was characterized by lower turbidity, higher percentage transmittance and better self-emulsifying properties, and based on the in vitro dissolution study it can be concluded that better solubilization properties were exhibited by solid formulation OF2. Overall, the studies demonstrated the possibility of formulating liquid and solid SEEDS as promising carriers of atorvastatin. SEDDS, with their unique solubilization properties, provide the opportunity to deliver lipophilic drugs to the gastrointestinal tract in a solubilized state, avoiding dissolution-a restricting factor in absorption rate of BCS Class 2 drugs, including atorvastatin.