Penetration enhancer-containing spanlastics (PECSs) for transdermal delivery of haloperidol: in vitro characterization, ex vivo permeation and in vivo biodistribution studies.
TL;DR: The biodistribution study showed that the transdermal 99mTc-SF hydrogel exhibited a more sustained release pattern and longer circulation duration with pulsatile behavior in the blood and higher brain levels than the oral 99mRq-SF dispersion.
Abstract: Haloperidol (Hal) is one of the widely used antipsychotic drugs. When orally administered, it suffers from low bioavailability due to hepatic first pass metabolism. This study aimed at developing Hal-loaded penetration enhancer-containing spanlastics (PECSs) to increase transdermal permeation of Hal with sustained release. PECSs were successfully prepared using ethanol injection method showing reasonable values of percentage entrapment efficiency, particle size, polydispersity index and zeta potential. The statistical analysis of the ex vivo permeation parameters led to the choice of F1L – made of Span® 60 and Tween® 80 at the weight ratio of 4:1 along with 1% w/v Labrasol® – as the selected formula (SF). SF was formulated into a hydrogel by using 2.5% w/v of HPMC K4M. The hydrogel exhibited good in vitro characteristics. Also, it retained its physical and chemical stability for one month in the refrigerator. The radiolabeling of SF showed a maximum yield by mixing of 100 µl of diluted formula wit...
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TL;DR: The in-vivo pharmacodynamic study showed that OF could result in higher reduction in IOP, significantly sustain that reduction inIOP and increase Dorz bioavailability compared to Trusopt® eye drops, which is very promising for being used in glaucoma treatment.
Abstract: Glaucoma is the second cause of blindness worldwide. Frequent administration of traditional topical dosage forms may lead to patient incompliance and failure of treatment. Our study aims to formula...
56 citations
Cites background or methods from "Penetration enhancer-containing spa..."
...Similarity factor (f2) was calculated to compare the release profiles of the OF-gel before and after sterilization via the following equation (Moore & Flanner, 1996; Fahmy et al., 2018):...
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...This leads to decrease in their apparent molecular weight and concentration (Fahmy et al., 2018)....
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...The model with the highest R2 value described the flow pattern of OF-gel (Fahmy et al., 2018)....
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...The model with the highest R(2) value described the flow pattern of OF-gel (Fahmy et al., 2018)....
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...…(f2) was calculated to compare the release profiles of the OF-gel before and after sterilization via the following equation (Moore & Flanner, 1996; Fahmy et al., 2018): f2 ¼ 50 log 1þ 1n Xn t¼1 ðRt TtÞ2 " # 0:5 100 8< : 9= ; (4) where n is the number of sampling points, Rt and Tt are the mean…...
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TL;DR: In-vivo pharmacodynamic study assured the improved ocular bioavailability of BRT selected formula when compared with Alphagan®P with relative AUC0–24 of 5.024 and 7.90 folds increase in the mean residence time (MRT).
Abstract: Brimonidine tartrate (BRT) is a hydrophilic α2 adrenergic agonist used for the treatment of glaucoma. Glaucoma is an ocular disease affecting the anterior segment of the eye requiring lifetime trea...
55 citations
TL;DR: The aim of this work is to improve BRT ocular bioavailability and prolong its intraocular pressure lowering effect by the preparation of BRT loaded cubosomes according to a d-optimal design.
46 citations
TL;DR: Results are promising for further investigation of this formula and may indicate that the smaller particle size aided more than higher entrapment in achieving a higher permeation for Hal of 3.5±0.2μg/cm2.
Abstract: Haloperidol (Hal) is a well-known typical antipsychotic. Hepatic first pass metabolism leads to its limited oral bioavailability. This study aimed at enhancing transdermal delivery of Hal via spanlastic formulae. Hal-loaded spanlastics of Span®60 and an edge activator (EA) were successfully prepared by ethanol injection method according to a 31.41 full factorial design. In this design, independent variables were X1, EA type, and X2, Span®60 to EA ratio. Y1, percentage entrapment efficiency (EE%); Y2, particle size (PS); Y3, deformability index (DI); and Y4, percentage drug released after 4h (Q4h), were chosen as dependent variables. The Fourier-transform infrared spectral analysis showed no considerable chemical interaction between Hal and the used excipients. Both factors affected significantly all the responses except DI. Desirability of each prepared formula was calculated based on maximizing EE% and Q4h and minimizing PS. Formula F6, with X1, Tween®80, and X2, 8:2, had the highest desirability value followed by F7, with X1, Tween®80, and X2, 6:4, and both were chosen as selected formulae (SF) for further investigation. F6 (having more entrapped Hal), F7 (of smaller PS), and Hal solution in propylene glycol were subjected to ex vivo permeation test through newborn rat skin. Both formulae showed marked enhancement in drug permeation compared with drug solution. The significantly higher Q36h and J36h of F7 from F6 may indicate that the smaller particle size aided more than higher entrapment in achieving a higher permeation for Hal of 3.5±0.2μg/cm2.h. These results are promising for further investigation of this formula.
34 citations
TL;DR: Results confirmed that the prepared novel fluidized spanlastics formulation holds great promise for the treatment of psoriasis, and its benefit should futuristically be investigated in other topical diseases.
32 citations
References
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TL;DR: A facile interpretation of a considerable body of skin permeability measurements is presented that very adequately describes the dependence of Kp upon permeant size and lipophilicity, generates parameters of considerable physicochemical and mechanistic relevance, and implies that the SC lipids alone can fully characterize the barrier properties of mammalian skin.
Abstract: Published permeability coefficient (Kp) data for the transport of a large group of compounds through mammalian epidermis were analyzed by a simple model based upon permeant size [molecular volume (MV) or molecular weight (MW)] and octanol/water partition coefficient (Koct). The analysis presented is a facile means to predict the percutaneous flux of pharmacological and toxic compounds solely on the basis of their physicochemical properties. Furthermore, the derived parameters of the model have assignable biophysical significance, and they provide insight into the mechanism of molecular transport through the stratum corneum (SC). For the very diverse group of chemicals considered, the results demonstrate that SC intercellular lipid properties alone are sufficient to account for the dependence of Kp upon MV (or MW) and Koct. It is found that the existence of an “aqueous-polar (pore) pathway” across the SC is not necessary to explain the Kp values of small, polar nonelectrolytes. Rather, their small size, and consequently high diffusivity, accounts for their apparently larger-than-expected Kp. Finally, despite the size and breadth of the data set (more than 90 compounds with MW ranging from 18 to >750, and log Koct ranging from −3 to + 6), the postulated upper limiting value of Kp for permeants of very high lipophilicity cannot be determined. However, the analysis is able to define the physicochemical characteristics of molecules which should exhibit these maximal Kp values. Overall, then, we present a facile interpretation of a considerable body of skin permeability measurements that (a) very adequately describes the dependence of Kp upon permeant size and lipophilicity, (b) generates parameters of considerable physicochemical and mechanistic relevance, and (c) implies that the SC lipids alone can fully characterize the barrier properties of mammalian skin.
1,339 citations
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1,192 citations
"Penetration enhancer-containing spa..." refers methods in this paper
...The release profile of the stored SF-gel was compared to the freshly prepared one according to the model independent mathematical approach of Moore & Flanner (1996)....
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TL;DR: The ‘acid mantle’ of the stratum corneum seems to be important for both permeability barrier formation and cutaneous antimicrobial defense, however, the origin of the acidic pH, measurable on the skin surface, remains conjectural.
Abstract: The ‘acid mantle’ of the stratum corneum seems to be important for both permeability barrier formation and cutaneous antimicrobial defense. However, the origin of the acidic pH, measurable on the skin
628 citations
TL;DR: Transfersomes were successfully used in animals and humans, also for the transcutaneous peptide and protein delivery, and the theoretical rational for this is described together with the corresponding experimental models and practical examples.
Abstract: Agents with MW > 50%) and reproducibly various agents (200 < or = MW < or = 10(6); lipophilic/hydrophilic) into the body. Transfersomes were successfully used in animals and humans, also for the transcutaneous peptide and protein delivery. The theoretical rational for this is described together with the corresponding experimental models and practical examples.
464 citations
"Penetration enhancer-containing spa..." refers background in this paper
...Also, in the intestine there may be a secondary uptake of the transdermally delivered radioactive complex by the intestinal Peyer's patches (Cevc, 1996, 2003)....
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TL;DR: Diclofenac association with ultradeformable carriers permits it to have a longer effect and to reach 10-times higher concentrations in the tissues under the skin in comparison with the drug from a commercial hydrogel, suggesting that dicl ofenac in Transfersomes has the potential to replace combined oral/topical dic lofenacs administration in humans.
359 citations
"Penetration enhancer-containing spa..." refers background in this paper
...These detected levels of the radioactive complex after transdermal application in the liver, stomach and the intestine may be because the localization of the complex is both formulation and application-site dependent (Cevc & Blume, 2001)....
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