Significance: UA is a potential phytoconstituent obtained from several plant sources, which has been explored for its diverse pharmacological activities including hepatoprotection. Its major limitation is poor absorption, rapid elimination, and hence low bioavailability after administration.
Methods: Response surface methodology was adopted to formulate an optimized (UA) complex. The complex was characterized by differential thermal analysis (DTA), Fourier transform-Infrared Spectroscopy, Powder X ray Diffraction, molecular docking, etc. The physico-chemical profile (solubility, oil/water partition coefficient) and in vitro dissolution profile was estimated. The formulation was then used to study hepatoprotective activity and bioavailability in animal models.
Results: Results showed that the phospholipid complex of UA has enhanced the hepatoprotective potential as compared to pure UA at the same dose level. The complex restored the levels of serum hepatic marker enzymes with respect to untreated group and increased the relative bioavailability of UA in rat plasma by 8.49-fold in comparison with pure compound at the same dose level. It enhanced the elimination half-life (t1/2 el) from 0.69 ± 1.76 to 8.28 ± 1.98 h.
Conclusion: Complexation of UA with phospholipid markedly enhanced the hepatoprotective potential of UA by improving its bioavailability and pharmacokinetic parameters.
Novelty statement
The present article deals with rational optimization of the formulation parameters for phospholipid complex of ursolic acid by Response Surface Methodology analysis, characterizing the formulation by in silico approach apart from conventional instrumental techniques, and evaluating the in vitro dissolution, pharmacokinetics, and hepatoprotective activity of the complex in animals.
Novelty statement
The present article deals with rational optimization of the formulation parameters for phospholipid complex of ursolic acid by Response Surface Methodology analysis, characterizing the formulation by in silico approach apart from conventional instrumental techniques, and evaluating the in vitro dissolution, pharmacokinetics, and hepatoprotective activity of the complex in animals. 相似文献
Significance: Various types of rubber closures with different compositions are available for drug packaging. Many additives of rubber closures can be released from rubber closures and may affect the quality of drugs and pose a risk to human health. In this study, we aimed to determine the relationship between cephalosporin structure, solution clarity, and rubber closure compatibility using volatile components profile of butyl rubber closures.
Methods: Two opposite polarity gas chromatography (GC) systems and GC-mass spectrometry (MS) were used to achieve rapid qualitative determination of the main volatile components in rubber closures. Simulated adsorption experiment was performed to investigate the adsorption of main volatile components in rubber closures by cephalosporins with different side chain structures, and to determine the effects of adsorption on solution clarity.
Results: A volatile components screening library of rubber closures was established and the structures of some volatile component were confirmed. The specific adsorption of the structure of cephalosporins on volatile components from rubber closures was studied.
Conclusion: Based on the results of this study, rubber closures with good compatibility for cephalosporins with different side chain structures can be selected rapidly. This experimental strategy not only facilitates the screening of suitable rubber closures more effectively, but also enables the quick determination of volatile components adsorbed by drugs. 相似文献
Significance: The presence of metal ions together with Cipro results in complexes exhibiting a decreased bioavailability. Attempts were made to better understand the mechanism of decreased Cipro bioavailability in the presence of metals such as calcium and ferrous ions, and a small-sized ligand citric acid (CitA).
Methods: Effect of complex size or other potential factors was studied using diffusion through synthetic membrane, permeation studies across Caco-2 cells and capillary electrophoresis. A molecular dynamics (MD) simulation study was conducted to find the arrangement and the nature of the interactions between Cipro molecules and ferrous ions.
Results: Cipro was shown to form complexes with metals and CitA. The presence of CitA improved permeation of Cipro through the synthetic membrane but this was not as obvious in case of Caco-2 cells. Capillary electrophoresis suggested the existence of large molecular aggregates of Cipro: metal complexes. MD simulations offered clear evidence of large size aggregates in line with the experimental findings. CitA alone significantly improved permeation of Cipro through Caco-2 cells.
Conclusions: The size of the formed complexes, rather than the decrease in the solubility of formed complexes, plays a significant role in permeation (absorption) of Cipro. CitA might ameliorate the effect of co-administered metal ions on the bioavailability of Cipro. 相似文献
Significance: Rhein is a potential candidate for the therapy of kidney disease. However, the poor solubility, inadequate bioavailability, and lack of proper formulation restrict its clinical applicability. LMWC-drug conjugates offer the potential to improve the water-solubility of RH, increase its oral absorption, and thereby enhance its bioavailability.
Methods: The conjugates were synthesized via a carbodiimide reaction and confirmed using UV-vis, FTIR, and 1H-NMR spectroscopy. The water-solubility and in vitro release properties were evaluated. Free RH and RH-LMWC conjugates were administered at an equivalent oral gavage dose of RH at 35?mg/kg for pharmacokinetic studies in Sprague Dawley rats.
Results: The conjugates with RH content of 9.65% were successfully synthesized and featured a satisfactory water-solubility of 9.73?mg/mL, which exhibited a sustained release pattern over 72?h, and the enzymes present may promote the degradation of the conjugate to increase the release of Rhein. Oral administration of RH-LMWC conjugates to rats led to seven-folds and 3.1-folds increase in the T1/2 and AUC0–∞, respectively, as compared to RH suspension.
Conclusion: The present work demonstrated that the RH-LMWC conjugates exhibited sustained release properties with outstanding oral bioavailability enhancements compared to administration of RH itself. Potentially, RH-LMWC conjugates may serve as a promising lead for developing a new platform for RH oral delivery. 相似文献
Significance: The sublingual cavity is an interesting route for administration of drugs with limited oral bioavailability due to hepatic first pass metabolism. By this route, the drug is directly absorbed into blood circulation. In this sense, mucoadhesive carvedilol-loaded nanocapsules (CAR-NC) were previously proposed for the administration of this drug by sublingual route. Carvedilol is used for cardiovascular diseases and suffers metabolism in liver when orally administrated. Nanoencapsulation of carvedilol controlled its permeation across porcine sublingual mucosa.
Methods: Carvedilol-loaded cationic nanocapsules were prepared by interfacial deposition of a preformed polymer. Drug permeation studies were carried out in Transwell® inserts. The integrity of cell monolayers after the drug transport was assessed by transepithelial electric resistance. Compatibility of the CAR-NC with the SCC4 cells was evaluated by the Sulforhodamine B assay.
Results: The drug permeated the cell monolayer by a controlled way when nanoencapsulated and this profile had a linear relation with those observed in porcine sublingual mucosa. The integrity of the cell monolayer was maintained after drug permeation and CAR-NC was no cytotoxic to SCC4 cells.
Conclusion: Nanoencapsulated carvedilol permeated by a controlled and safe way by SCC4 cell monolayer. SCC4 cells monolayers may be used as in vitro model for sublingual drug transport studies in the development of novel formulations. 相似文献
Significance: The use of predicted stability studies during pharmaceutical development and in regulatory submissions is increasing, particularly in early phase to support an initial retest period/shelf life claim in the absence of standard stability data. These studies offer an alternative to standard stability testing and can facilitate clinical trials to be started earlier and medicines to reach patients faster. They involve a short-term stressed stability study, typically designed to degrade a drug substance or product to the specification level of the shelf life limiting attribute. The results are used to predict degradation under long-term storage conditions and enable stability understanding to be gained over a short time frame, using limited amounts of material.
Methods: In this work, Accelerated Stability Assessment Program (ASAP) studies were performed for 10 different drug substances and the predictions obtained for chemical degradation were compared to ICH compliant stability data.
Results: Across the studies good agreement was achieved, with the initial retest period predictions from the ASAP studies being conservative by design. When minimal degradation was observed during an ASAP study, it was demonstrated that at least a 12-month initial retest period could be supported.
Conclusion: This comparison of ASAP predictions and ICH compliant stability data has demonstrated the ability of well-designed ASAP studies to predict the long-term chemical stability of drug substances. 相似文献
Significance: This study will provide an insight about the use of nanocarriers, esp. NLCs loaded with dithranol for the effective treatment of psoriasis.
Methods: Dithranol-loaded NLCs were prepared by hot melt homogenization method and characterized for particle size and percentage entrapment efficiency. The optimized NLCs were loaded into gel and evaluated for drug release, spreadability, rheological behavior, and staining. Anti-psoriatic efficacy of the NLC gel was evaluated in imiquimod (IMQ) induced psoriatic plaque model in comparison with prepared conventional ointment formulation (1.15% w/w dithranol).
Results: NLCs were prepared with particle size below 300?nm, polydispersity index (PDI) below 0.3 and percentage entrapment efficiency of ～100%. The prepared NLC gel was then compared with the ointment for drug release, staining property, and efficacy. Topical application of dithranol-loaded NLC gel on IMQ-induced psoriatic plaque model reduced the symptoms of psoriasis assessed by both Psoriasis area severity index (PASI) scoring and enzyme-linked immunosorbent assay. There was a significant reduction in disease severity and cytokines like Interleukins-17, 22, 23 and Tumor necrosis factor-α by the developed system in comparison to the negative control.
Conclusions: To conclude dithranol-loaded NLCs in gel base was efficacious in management of psoriasis at the same drug concentration and also offer less cloth staining to that of the ointment product. 相似文献
Significance: The current epidemiology of tuberculosis along with the increasing emergence of resistant forms of tuberculosis necessitates the need for developing alternative efficacious medicines for treatment. Licorice is a medicinal herb with reported activity against Mycobacterium tuberculosis.
Methods: Liposomes with LE were prepared by thin film hydration technique and freeze dried to obtain LDPI. The comprehensive in vitro and in vivo characterization of the LDPI formulation was carried out.
Results: The particle size of liposomes was around 210?nm with drug entrapment of almost 75%. Transmission electron microscopy revealed spherical shape of liposome vesicles. The flow properties of the LDPI were within acceptable limits. Anderson Cascade Impactor studies showed the mean median aerodynamic diameter, geometric standard deviation and fine particle fraction of the LDPI to be 4.29?µm, 1.23, and 54.68%, respectively. In vivo lung deposition studies of LDPI in mice showed that almost 46% of the drug administered reaches the lungs and 16% of administered drug is retained in the lungs after 24?hours of administration. The in vivo pharmacodynamic evaluation of the LDPI showed significant reduction in bacterial counts in lungs as well as spleen of TB-infected mice.
Conclusions: LE LDPI thus has a promising potential to be explored as an effective anti-tubercular medicine or as an adjunct to existing anti-tubercular drugs. 相似文献
Significance: Status epilepticus (SE) is a medical emergency, requires intravenous administration of diazepam which requires hospitalization of patient. Initiation of therapy at home via nasal administration of diazepam could prevent the damage of brain due to delay of therapy initiation.
Methods: Diazepam MEs were prepared by phase titration method, optimized by using Box–Behnken design. The influence of independent variables oleic acid, surfactant mixture (tween 80:propylene glycol), and water on dependent variables size, flux, and zeta potential was investigated. Optimized MEs, MMEs, and Calmpose (i.v route) were evaluated for pharmacokinetic and pharmacodynamic studies on rats.
Results: MME2 composed of oleic acid (5), surfactant mixture (50), water (45), and chitosan (0.5) showed size of 96.45?nm, PDI 0.21 and zeta potential 13.52?mV. MME2 showed significantly high flux of 846.96?±?34?µg/cm2/h and AUCbrain 1206.49?±?145.8. The drug targeting efficiency (314%) and direct nose-to-brain transport (68.1%) of MME2 were significantly high compared to Calmpose (i.v) and ME. The latency periods of minimal clonal seizures and generalized tonic–clonic seizures of MME2 was significantly increased (p?<?0.0001) compared to drug solution and Calmpose (i.v).
Conclusion: The brain uptake of diazepam from chitosan-based MMEs via nasal route is significantly high compared to i.v route. 相似文献
Objective: The present research work was aimed to formulate and investigate teriflunomide (TFM)-loaded intranasal (i.n.) nanostructured lipid carriers (NLC) for the treatment of multiple sclerosis (MS).
Methods: The TFM-loaded NLC (TFM-NLC) nanoparticles were prepared by melt emulsification ultrasonication method using biodegradable and biocompatible polymers. The Box–Behnken statistical design was applied to optimize the formulation. The optimized NLC formulation was subjected to evaluate for particle size, entrapment efficiency (%), in vitro and ex vivo permeation. The safety and efficacy of optimized formulations were demonstrated using pharmacodynamic, subacute toxicity and hepatotoxicity data.
Results: Experimental data demonstrated that optimized NLC formulation (F17) showed significant size (99.82?±?1.36?nm), zeta potential (?22.29?±?1.8?mV) and % entrapment efficiency (83.39?±?1.24%). Alternatively, ex vivo permeation of TFM mucoadhesive NLC (TFM-MNLC) and TFM-NLC was observed 830?±?7.6 and 651?±?9.8?µg/cm2, respectively. Whereas, TFM-MNLC shows around 2.0-folds more Jss than the TFM-NLC. Finally, TFM-MNLC (i.n.) formulation produced the rapid remyelination in cuprizone-treated animals and decreases the number of entries in open compartment of EPM when compared with negative control and TFM-NLC (oral) animals. Simultaneously, the nanoformulation did not reflect any gross changes in hepatic biomarkers and subacute toxicity when compared with control.
Conclusions: Hence it can be inferred that the nose-to-brain delivery of TFM-MNLC can be considered as effective and safe delivery for brain disorders. 相似文献
Methods: Indinavir-loaded nanoemulsions (IDV-NEs) were prepared by high-speed homogenization method, and then lactoferrin was coupled to IDV-NEs by water soluble EDC method.
Results: The hydrodynamic diameters, polydispersity index, and zeta potential of IDV-NEs were 112?±?3.5?nm, 0.20?±?0.02, and ?33.2?±?2.6?mV, respectively. From in vivo studies in animal model of rats, the AUC0–4?h of brain concentration–time profile of IDV-NEs and Lf-IDV-NEs were 1.6 and 4.1 times higher than free drug, respectively. The brain uptake clearance of IDV-NEs and Lf-IDV-NEs were, interestingly, 393- and 420-times higher than the free drug.
Conclusions: It can be concluded that applying both lactoferrin-treated and non-treated nanoemulsions clearly leads to significant brain penetration enhancement of indinavir, an effect which is more pronounced in the case of Lf-IDV-NEs with the higher drug residence time in brain. 相似文献
Significance: Poor aqueous solubility of PGH was overcome by the design of SDs. Level A correlation demonstrated between in vitro release and bioavailability of PGH, suggest its biowaiver potential.
Methods: The effects of semicrystalline copolymers (poloxamer 407 and gelucire 50/13) and methods of preparations on dissolution behavior, in vivo performance, and stability of PGH SDs were investigated. All the SDs were characterized by FTIR, TGA, DSC, XRD, and SEM.
Results: FTIR and TGA showed the compatibility with the polymers. The significant change in melting pattern of the PGH observed in the DSC thermograms supported by XRD patterns & SEM indicated a change from a crystalline to an amorphous state. Gelucire 50/13 was observed to have greater ability to form SDs than poloxamer 407 in solvent evaporation method (SM). Prevention of recrystallization during storage suggested stability of the formulation. Gelucire 50/13 based SD, prepared by SM remarkably increased the dissolution within 15?min (87.27?±?2.25%) and was supported by dissolution parameters (Q15, IDR, RDR, % DE, f1, f2). These SDs showed pH-dependent solubility. In vivo test showed significantly (p?<?.05) higher AUC0–t and Cmax, which were about 3.17 and 4.34 times that of the pure drug respectively.
Conclusion: Gelucire 50/13 was found to be a suitable carrier for SM for preparation of SDs of PGH as evident from increased dissolution and bioavailability. 相似文献
Significance: Published studies have investigated the reflux-suppressing alginate component of Gaviscon Double Action (Gaviscon DA; RB, UK) but intragastric acid neutralization activity of the antacid component has not been evaluated in vivo.
Methods: Intragastric pH monitoring, using a custom-made 10-electrode catheter, was evaluated in a two-part exploratory study in healthy subjects; Part I (n?=?6) tested suitability of the catheter using antacid tablets (Rennie; Bayer, Germany); Part II (n?=?12) evaluated gastric acid neutralization activity of Gaviscon DA liquid (20?ml) versus placebo in fasted subjects using a randomized, open-label, crossover design. The primary endpoint was the percentage of time that intragastric pH ≥4 was measured during 30?min post-treatment. A confirmatory study of identical design was subsequently conducted (n?=?20).
Results: Monitoring pH using the multielectrode catheter was a viable approach, directly detecting changes in intragastric pH following a single dose of antacid tablets. In the exploratory study, the percentage of time that pH ≥4 during 30?minutes post-treatment was 46.8% with Gaviscon DA liquid versus 4.7% with placebo (p?=?0.0004). These findings were supported by the confirmatory study, where pH ≥4 was recorded 50.8% of the time with Gaviscon DA versus 3.5% with placebo (p?=?0.0051). In this study, Gaviscon DA was safe and well tolerated.
Conclusions: These studies demonstrate the effective acid neutralizing capacity of Gaviscon DA versus placebo in healthy, fasted subjects. This adds to the evidence base for the combination of alginates and antacids. 相似文献
Significance: Nanosized carrier systems, as niosomes would provide great potential for improving NAT ocular bioavailability.NAT niosomal dispersion formulae were prepared and then incorporated in 0.5%KT gels using different mucoadhesive viscosifying polymers.
Methods: Niosomes were prepared using the reverse-phase evaporation technique. In vitro experimental, and in vivo clinical evaluations for these formulations were done for assessment of their safety and efficacy for treatment of Candida Keratitis in Rabbits. In vitro release study was carried out by the dialysis method. In vivo and histopathological studies were performed on albino rabbits.
Results: NAT niosomes exhibited high entrapment efficiency percentage (E.E%) up to96.43% and particle size diameter ranging from 181.75?±?0.64 to 498.95?±?0.64?nm, with negatively charged zeta potential (ZP). NAT niosomal dispersion exhibited prolonged in vitro drug release (40.96–77.49% over 24h). NAT-loaded niosomes/0.5%KT gel formulae revealed retardation in vitro release, compared to marketed-product (NATACYN®) and NAT-loaded niosomes up to57.32% (F8). In vivo experimental studies showed the superiority for F8 in treatment of candida keratitis and better results on corneal infiltration and hypopyon level. These results were consistent with histopathological examination in comparison with F5 and combined marketed products (NATACYN® and Ketoroline®).
Conclusions: This study showed that F8 has the best results from all pharmaceutical in vitro evaluations and a better cure percent in experimental application and enhancing the prolonged delivery of NAT and penetrating the cornea tissues. 相似文献
Significance: Dual cross-linked CS microspheres developed by the spray-drying technique displays significantly higher level of sustained drug release compared with non-cross-linked CS microspheres.
Methods: LF-loaded CS microspheres were prepared using the spray-drying technique, and then solidified with tripolyphosphate and glutaraldehyde as dual cross-linking agents. The microspheres were characterized by surface morphology, size distribution, zeta potential, encapsulation efficiency, and drug release profiles in vitro. The drug quantification was verified and analyzed by high-performance liquid chromatography (HPLC). The structural interactions of the CS with LF were studied with Fourier transform infrared spectroscopy. The effect of various influencing excipients in the formulation of the dual cross-linked CS microspheres on drug encapsulation efficiency and the drug release profiles were extensively investigated.
Result: The microspheres demonstrated high encapsulation efficiency (72.4?～?98.55%) and were uniformly spherical with wrinkled surface. The mean particle size was between 1020.7?±?101.9 and 2381.2?±?101.6?nm. All microspheres were positively charged (zeta potential ranged from 31.1?±?1.32 to 42.81?±?1.55?mV). The in vitro release profiles showed a sustained release of the drug and it was remarkably influenced by the cross-linking process.
Conclusion: This novel spray-drying technique we have developed is suitable for manufacturing LF-loaded CS microspheres, and thus could serve as a potential platform for sustained drug release for effective therapeutic application in ocular infections. 相似文献
Significance: Colloidal aqueous dispersions of lyotropic liquid crystal mesophases such as the identified as cubosomes and hexosomes, and so on, have received considerable attention due to their unique nanostructures and their thermodynamic properties, which provide the potential as a sustained drug release matrix. Additionally, their large surface area and similarity with the liquid crystal structures of intercellular lipids of stratum corneum enhances the interaction with the skin and mucous, increasing the potential for topical drug delivery efficiency of biopharmaceutical class II drugs as the antifungal ketoconazole.
Methods: This article presents the results in morphological characteristics, particle size, ζ potential, flow, thermal behavior and drug release studies of hexosomes containing ketoconazole (LHLC-K) obtained with glycerol monooleate, propylene glycol monolaurate, poloxamer, and water mixtures.
Results: This colloidal system exhibits a Newtonian-type flow and a hexagonal nanostructure with a median particle size of 107?±?20?nm and ζ potential of +4.45?±?0.50?mV. Through differential scanning calorimetry studies, the LHLC-K demonstrated physical and chemical stability for more than six months and mesophasic thermal reversibility between 10 and 50?°C. Finally, LHLC-K releases ketoconazole following a kinetics described by the first order model.
Conclusions: Physicochemical properties of the hexosomes containing ketoconazole are important for topical mycosis treatment administration, conditions of storage, and for its incorporation into the formulation of semi-solid dosage forms. 相似文献
Significance: Understanding the attributes that affect drug release from gelatin matrix could provide the knowledge base for the development, manufacturing, and performance evaluation of gelatin-based drug products for sustained drug delivery.
Methods: Chlorhexidine (CHX) was the model drug in the gelatin-product testing. The gelatin products were fabricated by two methods: a single-pot mixing of all the components and a two-step gelatin crosslinking followed by drug loading. Different gelatin types (Type A porcine and Type B bovine), glutaraldehyde (GTA) crosslinking conditions, glycerin concentration, and CHX concentration in drug loading and loading time were used to fabricate the products. The cumulative amounts of CHX release from the gelatin products were determined using in vitro release testing (IVRT).
Results: The attributes affecting CHX release from the gelatin products were gelatin type, GTA crosslinking, and CHX loading concentration. The fabrication methods (two-step method of gelatin crosslinking and drug loading by equilibration vs. direct mixing of the components) also affected CHX release. Other attributes such as glycerin and CHX loading time did not show significant effects on drug release under the conditions studied. In addition, the results in the two IVRT methods employed in this study were comparable.
Conclusion: Gelatin products of qualitative (Q1) and quantitative (Q2) differences could lead to different drug release behaviors. Drug release was also affected by the ingredient mixing steps during gelatin chip fabrication. 相似文献
Significance: FDC has been proven effective in improving patient compliance for treatment that requires complex multidrug regimen. Currently, there is growing interest to develop FDC of poorly-soluble drugs due to the increased number of drugs exhibiting poor solubility thus low bioavailability.
Methods: The dual-drug nanoplex was prepared by electrostatically-driven co-complexation of drug molecules with oppositely charged dextran sulfate, using ciprofloxacin (CIP) and itraconazole (ITZ) as the model poorly-soluble drugs.
Results: We first verified that the co-complexation products were dual-drug CIP-ITZ nanoplex, and not binary mixtures of the single-drug CIP and ITZ nanoplexes, by demonstrating their distinct thermal behaviors and dissolution characteristics. Depending on the preparation condition, the dual-drug nanoplex exhibited size and zeta potential of 160–410?nm and ?35–50?mV, respectively. The individual drug payloads were readily manipulated by varying the CIP/ITZ mass ratio in the feed, resulting in CIP and ITZ payloads in the range of 60-30% and 15-45%, respectively. The CIP-ITZ nanoplex, however, exhibited diminished CIP supersaturation generation, thus lower CIP solubility enhancement, compared to the single-drug CIP nanoplex. The CIP-ITZ nanoplex, nonetheless, remained capable of generating high ITZ supersaturation level.
Conclusion: Dual-drug nanoplex was successfully prepared with a high degree of control over its physical characteristics. Nevertheless, whether dual-drug nanoplex always exhibits diminished solubility enhancement compared to its single-drug counterparts needs to be investigated using different poorly-soluble drugs. 相似文献
Methods: 3(2) factorial design and response surface methodology was utilized to prepare formulations by intercalating the varied concentration of polymers(A) and penetration enhancer(B) in solvent. The effect of these independent factors on drug release and flux was investigated to substantiate the ex-vivo, stability and histological findings of the study.
Results: FTIR, DSC revealed the compatibility of drug with polymers; however, the semicrystallinity in drug was observed under PXRD. SEM micrographs showed homogeneous dispersion and entanglement of drug throughout the matrix. Results from the permeation study suggested the significant effect of factors on the ex vivo permeation of drug. It was observed that drug release was found to be increased with an increase in hydrophilic polymer concentration and PE. The formulations having polymers (EC:PVPK-30) at 7:3 showed maximum drug release with highest flux (102.60?±?1.12?µg/cm2/h) and permeability coefficient (32.78?±?1.38?cm/h). Significant effect of PE on lipid and protein framework of the skin was also observed which is responsible for increased permeation. The optimized formulation was found to be stable and showed no-sign of localized reactions, indicating safety and compatibility with the skin.
Conclusion: Thus, results indicated that the prepared intercalated transdermal matrix can be a promising nonoral carrier to deliver effective amounts of drug. 相似文献