A correlative model to predict in vivo AUC for nanosystem drug delivery with release rate-limited absorption

Purpose. Drug release from nanosystems at the sites of either absorption or effect biophase is a major determinant of its biological action. Thus, in vitro drug release is of paramount importance in gaining insight for the systems performance in vivo. Methods. A novel in vitro in vivo correlation, IVIVC, model denoted as double reciprocal area method was presented and applied to 19 drugs from 55 nano formulations with total 336 data, gathered from literature. Results. The proposed model correlated the in vitro with in vivo parameters with overall error of 12.4 ± 3.9%. Also the trained version of the model predicted the test formulations with overall error of 15.8 ± 3.7% indicating the suitability of the approach. A theoretical justification was provided for the model considering the unified classical release laws. Conclusion. The model does not necessitate bolus intravenous drug data and seems to be suitable for IVIVC of drugs with release rate-limited absorption

Kinetic analysis of drug release from nanoparticles

PURPOSE. Comparative drug release kinetics from nanoparticles was carried out using conventional and our novel models with the aim of finding a general model applicable to multi mechanistic release. Theoretical justification for the two best general models was also provided for the first time. METHODS. Ten conventional models and three models developed in our laboratory were applied to release data of 32 drugs from 106 nanoparticle formulations collected from literature. The accuracy of the models was assessed employing mean percent error (E) of each data set, overall mean percent error (OE) and number of Es less than 10 percent. RESULTS. Among the models the novel reciprocal powered time (RPT), Weibull (W) and log-probability (LP) ones produced OE values of 6.47, 6.39 and 6.77, respectively. The OEs of other models were higher than 10%. Also the number of errors less than 10% for the models was 84.9, 80.2 and 78.3 percents of total number of data sets. CONCLUSIONS. Considering the accuracy criteria the reciprocal powered time model could be suggested as a general model for analysis of multi mechanistic drug release from nanoparticles. Also W and LP models were the closest to the suggested model RPT

Studies on Dissolution Enhancement of Prednisolone, a Poorly Water-Soluble Drug by Solid Dispersion Technique

Introduction: Prednisolone is a class II substance according to the Biopharmaceutics Classification System. It is a poorly water soluble agent. The aim of the present study was to improve dissolution rate of a poorly water-soluble drug, prednisolone, by a solid dispersion technique. Methods: Solid dispersion of prednisolone was prepared with PEG 6000 or different carbohydrates such as lactose and dextrin with various ratios of the drug to carrier i.e., 1:10, 1:20 and 1:40. Solid dispersions were prepared by coevaporation method. The evaluation of the properties of the dispersions was performed using dissolution studies, Fourier-transform infrared spectroscopy and x-ray powder diffractometery. Results: The results indicated that lactose is suitable carriers to enhance the in vitro dissolution rate of prednisolone. The data from the x-ray diffraction showed that the drug was still detectable in its solid state in all solid dispersions except solid dispersions prepared by dextrin as carrier. The results from infrared spectroscopy showed no well-defined drug–carrier interactions for coevaporates. Conclusion: Solid dispersion of a poorly water-soluble drug, prednisolone may alleviate the problems of delayed and inconsistent rate of dissolution of the drug

Preparation of Gliclazide Nanoparticles via Electrospraying Method and Evaluation of Their Physicochemical Properties

Introduction:  Gliclazide is a second-generation sulfonylurea used in the treatment of non-insulin dependent diabetes mellitus. Gliclazide is practically insoluble in water, therefore, researchers try to find techniques to improve its physicochemical properties. On the other hand, researches has shown that nanoparticles are effective in improving the physicochemical characteristics of poorly water-soluble drugs. There are many methods to prepare nanoparticles, among all, electrospraying as a one-step and cost-benefit technique can  be easily applied in industrial scale. Methods and Results:  Gliclazide and polymer (Eudragit RS100 or PEG6000) were co-dissolved in acetone with drug: polymer ratios of 1:5 and 1:10, so that the polymer solution concentrations were 10, 15 and 20% (w/v). Then these solutions were electosprayed. The particle size and morphology were evaluated using scanning electron microscopy (SEM). The physicochemical characteristics of nanofibers and nanoparticles were evaluated by DSC thermograms, FTIR spectroscopy and X-Ray crystallography. Drug release profiles were studied as well. The size of prepared nanofibers and nanobeads, ranged from 100 nm-500 nm. Based on the physicochemical characteristics, there was a transition from crystalline to amorphous state of Gliclazide. No interaction between drug and polymers were observed in the prepared nanoparticles. In vitro drug release studies revealed that the drug-release patterns were improved in the prepared nanoparticles. Conclusions:  Electrospraying is a simple and low-cost method that can be used to produce Gliclazide nanoparticles in industrial scale and improve physicochemical properties of the drug

Morphological and Physicochemical Evaluation of Modafinil-Eudragit RS100 Nanoformulations Prepared by Electrospray Method

Introduction: Modafinil is a wake-promoting agent approved by FDA for the treatment of narcolepsy and shift work sleep disorder. Due to its insolubility in water, the drug exhibits low oral bioavailability. Studies have shown that formulating poorly-soluble drugs as nanoparticles can improve the drugs physicochemical properties. Electrospraying is an uncomplicated and cost-benefit method for preparing nanoparticles that can easily be scaled up. Methods and Results: Modafinil and Eudragit RS100 were co-dissolved in methanol and acetone (1:1) with the drug: polymer ratios of 1:5 and 1:10 at various total solution concentrations (10%, 15% and 20%). The solutions were injected through a capillary tube on a Teflon screen at a rate of 2 ml/h. A voltage of 20-25 kV was applied between the injection needle and the Teflon screen. The particle size and morphology of resultant nanoparticles and nanofibers were evaluated via scanning electron microspore (SEM). Thermal behavior and crystallinity of the samples were studied by differential scanning calorimeter (DSC) and Powder X-ray diffraction (PXRD). Fourier transform infrared spectroscopy (FTIR) was used to determine any possible interaction between the drug and the polymer. In vitro drug release profile was studied at a pH of 6.8 via USP apparatus II. SEM results suggested that solutions with lower concentration created nanoparticles (100-300 nm) while increasing the concentration resulted in formation of nanofibers (50-100 nm). DSC and PXRD analysis revealed that electrosprayed Modafinil was transferred from crystalline to amorphous state. FTIR results indicated that hydrogen bonds might have formed between the drug and polymer. Drug release profile revealed that electrospraying process modified drug release pattern. Some of the formulations managed to increase the release rate whereas other formulations resulted in slower release. Conclusions: Electrospraying is a suitable method for fabricating nanofibers and nanoparticles of Modafinil. The resultant nanoformulations show properties such as reduced size, decreased crystallinity and modified release rate, thus help Modafinil to have higher oral bioavailability

Recent advances in improving oral drug bioavailability by cocrystals

Introduction: Oral drug delivery is the most favored route of drug administration. However, poor oral bioavailability is one of the leading reasons for insufficient clinical efficacy. Improving oral absorption of drugs with low water solubility and/or low intestinal membrane permeability is an active field of research. Cocrystallization of drugs with appropriate coformers is a promising approach for enhancing oral bioavailability. Methods: In the present review, we have focused on recent advances that have been made in improving oral absorption through cocrystallization. The covered areas include supersaturation and its importance on oral absorption of cocrystals, permeability of cocrystals through membranes, drug-coformer pharmacokinetic (PK) interactions, conducting in vivo-in vitro correlations for cocrystals. Additionally, a discussion has been made on the integration of nanocrystal technology with supramolecular design. Marketed cocrystal products and PK studies in human subjects are also reported. Results: Considering supersaturation and consequent precipitation properties is necessary when evaluating dissolution and bioavailability of cocrystals. Appropriate excipients should be included to control precipitation kinetics and to capture solubility advantage of cocrystals. Beside to solubility, cocrystals may modify membrane permeability of drugs. Therefore, cocrystals can find applications in improving oral bioavailability of poorly permeable drugs. It has been shown that cocrystals may interrupt cellular integrity of cellular monolayers which can raise toxicity concerns. Some of coformers may interact with intestinal absorption of drugs through changing intestinal blood flow, metabolism and inhibiting efflux pumps. Therefore, caution should be taken into account when conducting bioavailability studies. Nanosized cocrystals have shown a high potential towards improving absorption of poorly soluble drugs. Conclusions: Cocrystals have found their way from the proof-of-principle stage to the clinic. Up to now, at least two cocrystal products have gained approval from regulatory bodies. However, there are remaining challenges on safety, predicting in vivo behavior and revealing real potential of cocrystals in the human

Nano-suspension coating as a technique to modulate the drug release from controlled porosity osmotic pumps for a soluble agent

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The effect of chamomile intake on lipid profile in patients with diabetes and related metabolic disorders. A systematic review and meta-analysis of randomized controlled trials

Background. The current study sought to provide a robust examination of the evidence for the efficacy of chamomile on lipid profile in diabetics. Methods. PubMed, Scopus, web of Science, and Cochrane Library were systematically searched to find randomized controlled trials (RCTs) assessing the impact of chamomile intake on lipid profile, up to 17 August 2020. To obtain weighted mean difference (wMD) and 95% confidence intervals (CIs), a random-effects model was applied. A random-effects meta-regression was ran to detect the potential source of inter-study heterogeneity. Publication bias was checked using begg’s and Egger’s tests. Results. Four trials, comprising 254 participants, were included to the meta-analysis. In comparison with controls, total cholesterol (TC) (wMD = –22.40, 95% CI = = [–37.85, –6.96], P = 0.004, I2 = 59.1%) was significantly decreased in the groups receiving chamomile. In contrast, serum triglycerides (Tg) (wMD = –17.47, 95% CI = [–44.44, 9.50], P = 0.20, I2 = 74.3%), high density lipoproteins cholesterol (HDl-C) (wMD = 0.63, 95% CI = [–1.38, 2.64], P = 0.53, I2 = 0.0%), and low density lipoprotein cholesterol (lDl-C) (wMD = –10.94, 95% CI = [–23.71, 1.81], P = 0.09, I2 = 71.3%) were not significantly altered by chamomile consumption. Conclusion. The present meta-analysis demonstrates that chamomile can elicit significant reductions in serum TC, but not Tg, HDl-C and lDl-C in diabetics. Moreover, further large-scale and well-designed RCTs are required to confirm the veracity of these findings. (Clin Diabetol 2021; 10; 4: 375–381)</p