Maximization of the In Vitro transcorneal release and the In Vivo IOP-lowering effects of Latanoprost Ophthalmic gel formulations using Azone as a penetration enhancer and Carbopol-974 as a mucoadhesive

The objectives of this study were to maximize; a) the in vitro transcorneal release, b) the IOP-lowering effect and, c) the duration of action, of Latanoprost acid (LAT) ophthalmic gels. Method. The in vitro transcorneal release of LAT from a 1st set of gel formulations that containing different concentrations of Azone™ (as enhancer) with fixed concentration of C-974® (as mucoadhesive) were studied. Then, formulation that showed greatest permeability parameters at lowest Azone™ concentration was selected for preparation of a 2nd set of ocular gels containing various C-974® concentrations. Similarly, their in vitro permeabilities were evaluated, and the best C-974® concentration required for preparation of formulation(s) that can be conceded as ideal ophthalmic LAT gel(s) was pinpointed.  Thereafter, the in vivo IOP-lowering efficacy study for the scaled-up formulations from both sets of the test formulations was conducted using TONO-PEN™ AVIA tonometer in rabbits for 4-consecutive days. Finally, how long such IOP-lowering effect does persist?  To answer this question, the most effective formulations were used for a single-dose study, and the IOP was assessed at predetermined time interval till re-establishing the IOP base-line. Results. Majority of tested formulations have showed significant but varied augmentations in both, in vitro and in vivo results. Formulations (GAZ-4) & GC-4 have shown the highest therapeutic IOP lowering effects; i.e., (7.8±1.8), (6.5±2.1), respectively. Particularly noteworthy with both formulations the IOP base-line didn’t re-established after 24 hours, and their durations of action in the single-dose study were 47±2.25, and 48±1.5, respectively. Conclusion. The in vitro release, onset, magnitude & duration of action of action of LAT gels have been enhanced and extended for up to 2-day with two gel formulations.  Nonetheless, the success in developing a novel ophthalmic formulation depended for great extent upon the crucial net outcomes of a very sensitive interplay/balance between the drug and additives

Concentration-dependent enantioselective transport of chiral timolol maleate across hairless mice skin upon using various concentrations of chiral terpene enhancer (DLimonene)

The objective of the present study was to examine the relationship between different concentrations of the chiral enhancer D-Limonene (D-LM) on the solubility of individual enantiomers and racemate Timolol maleate (TM). The preferential improvement of D-LM on S-TM, R-TM, and racemate transported across the hairless mice skin was also investigated. For solubility studies, excess of R-, S-, or racemate with different concentrations of D-LM were prepared. The samples were agitated, centrifuged, filtered and analyzed using HPLC with a chiral column at a wavelength of 294 nm. For skin transport studies, formulations containing 0.5% solutions of S-TM, R-TM, or racemate in a buffer solution with predetermined concentrations of D-LM were studied. Samples of 1 ml were withdrawn and quantitatively analyzed for their TM contents. Steady-state fluxes (Jss), permeability coefficients and the enhancement factor were calculated. The studies showed that D-LM significantly increased the solubility of the enantiomeric, as well as, the racemate forms of TM in a concentration dependent manner. The permeation studies showed that the presence of D-LM significantly increased the flux values of both enantiomers and racemate. However, D-LM preferentially increased the permeability characteristics of the S-isomer compared to those of the R-isomer. Solubilities of the enantiomeric and the racemate forms of TM were found to be a singlevalued function of D-LM concentration. Moreover, the addition of D-LM increased the transport of the S-TM, R-TM enantiomers and the racemate across the hairless mice skin. In conclusion, all the tested formulations, the overall permeability characteristics of the therapeutically active TM (i.e., S-TM) proved to be superior to those obtained with the R-TM either as enantiomer or racemate

SCREENING STUDY FOR FORMULATION VARIABLES IN PREPARATION AND CHARACTERIZATION OF CANDESARTAN CILEXETIL LOADED NANOSTRUCTURED LIPID CARRIERS

Objective: The current study inspects the screening of the formulation components further, evaluates the physicochemical properties of the nanostructured lipid carriers (NLCs) for the antihypertensive drug as Candesartan Cilexetil (CC). The sequence screening of all excipients required for the preparation of NLCs should be performed. Methods: The prepared formulations were investigated for the different quality issues. The screening studies were performed to select the appropriate one of solid lipid, liquid lipid and surfactant. Also, investigation of physical compatibilities of solid lipid with liquid lipid and the ratios of them were evaluated. Furthermore, the physical characterization and quality issues of developed formulations were described and determined. Firstly, the solubility of CC in different solid and liquid lipids is the major parameter for the selection of the best one. Results:  Precirol® ATO 5, Compritol ® 888 ATO and Glyceryl Monostearate (GMS) were showed the maximum solubility of the CC (1000±4.12 mg, 1500±4.15 mg and 1750±3.16 mg), respectively. Hence, they were selected as the solid lipids for the development of NLCs. Liquid lipids Transcutol® HP (30±2.21 mg/ml), Labrasol® ALF (25±1.32 mg/ml) and CapryolTM 90 (18±1.34 mg/ml) were observed to have good affinity for the drug on systematic screening of different liquid lipids. All designed formulations observed in nanometer size of particles ranged from (408.9±11.5 to 114.6±8.3 nm) with high encapsulation efficiency around 99%.Also, the obtained results revealed that the ZP of the various formulations was consistently negative surface charge in between ((-13±2.3 to27.3±3.7 mV). Conclusion: Finally, formula number nine of CC (CC-NLC9) which composed of GMS (solid lipid), CapryolTM 90 (liquid lipid) and Lutrol® F127: Cremophore® RH (surfactants combination) was selected as the best formulation after the rank order for further investigations in the next work.  The current work clarifies a sequence steps for selection of excipients for NLCs by employing simple experiments.                                  Peer Review History: Received 20 December 2019;   Revised 5 January; Accepted 11 January, Available online 15 January 2020 Academic Editor: Ahmad Najib, Universitas Muslim Indonesia,  Indonesia, [email protected] UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file:                Reviewer's Comments: Average Peer review marks at initial stage: 5.0/10 Average Peer review marks at publication stage: 7.5/10 Reviewer(s) detail: Dr. Mohammed Abdel-Wahab Sayed Abourehab, Umm Al-Qura University; Makkah Al-Mukarramah, Saudi Arabia, [email protected] Dr. Maha Khalifa Ahmed Khalifa, Al-Azhar Universit - Cairo, Egypt, [email protected]  Dr. Evren Alğin Yapar, Turkish Medicines and Medical Devices Agency, Turkiye, [email protected]  Similar Articles: FORMULATION AND CHARACTERIZATION OF TOPICAL NANO EMULGEL OF TERBINAFINE A REVIEW ON GOLD NANOPRTICLES SYNTHESIS AND CHARACTERIZATION FORMULATION AND EVALUATION OF ELASTIC LIPOSOMES OF DECITABINE PREPARED BY ROTARY EVAPORATION METHO

RIBAVIRIN LOADED ERYTHROCYTES BY ENDOCYTOSIS AS TARGETED DRUG CARRIER SYSTEM

Objectives: Loaded erythrocytes, as drug carrier system, have tremendous potential to carry outside specificity and sustained release of drug. Thereby, enhancing therapeutic index and minimize the dose and adverse effects as well as improvement patient compliance. In the present paper, erythrocytes loaded Ribavirin with the aim to benefit the reticuloendothelial system targeting potential of the carrier cells. Methods: Endocytosis technique was used for Ribavirin loading in erythrocytes and the entire loading procedure was evaluated and validated. The in-vitro release of carrier erythrocytes was characterized, as well as the hematological indices, osmotic fragility and SEM analysis. Results: The maximum loaded amount and entrapment efficiency were found to be 9.58±0.045 mg and 38.3% at 25mg/ml of Ribavirin concentration after 60 minutes incubation time at 37oC with 88.42% cell recovery. The in-vitro Ribavirin release was found to obey Higuchi diffusion kinetics. Hematological parameters of Ribavirin loaded erythrocytes were significantly differ from native erythrocytes at (p≤ 0.01). Conclusion: The highly changed erythrocyte shape and morphology being one of the main determinants in erythrocytes disappearance kinetics in circulation, can be potentially beneficial in terms of successful cell targeting to the reticulo endothelial system which in turn leads to the improved Ribavirin effects on RES-mediated immune responses.           Peer Review History: Article received on- 3 October; Revised on- 22 October; Accepted on- 5 November, Available online 15 November 2016 Academic Editor: Dr. Asia Selman Abdullah, Al-Razi university, Department of Pharmacy, Yemen, [email protected] Received file:        Reviewer's Comments: Average Peer review marks at initial stage: 6.5/10 Average Peer review marks at publication stage: 8.0/10 Reviewer(s) detail: Dr. A.K. Rai, PSIT, Kanpur, U.P, India, [email protected] Dr. Sally A. El-Zahaby, Pharos University in Alexandria, Egypt, [email protected]

EFFECT OF PEGYLATED EDGE ACTIVATOR ON SPAN 60 BASED- NANOVESICLES: COMPARISON BETWEEN MYRJ 52 AND MYRJ 59

Objective: In recent years, Span 60 based nanovesicles have been the object of growing scientific attention as an alternative potential drug delivery system to conventional liposomes. Surface modification of nanovesicles can adjust the drug release rate and the affinity for the target site. The aim of present work was firstly to study the effects of different PEGylated edge activator (Myrj 52 and Myrj 59) on Span 60 based nanovesicles.Methods: Nanovesicles were prepared using Span 60 alone or in combination with Myrj 52 (polyethylene glycol 2000 monostearate) or Myrj 59 (polyethylene glycol 4400 monostearate) by employing the ethanol injection method. Myrj 52 and Myrj 59 are hydrophilic nonionic surfactants were used to modify the surface of the developed vesicles. Dynamic light scattering was used to determine the size, zeta potential and polydispersity index of the nanovesicles formulation. The vesicles were also characterized for entrapment efficiency and in vitro release.Results: In current work, the modified nanovesicles size (ranging from 54.32 to 141.7 nm), zeta potential (ranging from -5.67 to -27.1 mV) and polydispersity index (ranging from0.248 to 0.531) indicated that the surface modified nanovesicles vesicles are a homogenous and mono-disperse nanovesicles dispersions. The non-modified nanovesicles are showed higher particles size (>2 times) compared to modified nanovesicles. The modified nanovesicles were showed entrapment efficiency ranging from 36.42 to 78.13 %. All the modified nanovesicles showed accepted in vitro release of TN from nanovesicles (>70% released after 8 h), followed Higuchi models as drug release mechanism.Conclusion: In conclusion, these surface modified nanovesicles could be used as a potential drug carrier for a variety of drugs.                     Peer Review History: Received 16 July 2019;   Revised 12 August; Accepted 9 September, Available online 15 September 2019 Academic Editor: Prof. Dr. Gorkem Dulger, Duzce University, Turkey, [email protected] UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file:                Reviewer's Comments: Average Peer review marks at initial stage: 6.5/10 Average Peer review marks at publication stage: 9.5/10 Reviewer(s) detail: Dr. Robert Tungadi, State University of Gorontalo, Indonesia, [email protected] Prof. Dr. Kapil Kumar, Global Institute of Pharmaceutical Education and Research, Kashipur, US Nagar, Uttarakhand, India, [email protected] Similar Articles: SCREENING STUDY FOR FORMULATION VARIABLES IN PREPARATION AND CHARACTERIZATION OF CANDESARTAN CILEXETIL LOADED NANOSTRUCTURED LIPID CARRIER

Maximization of the in vitro transcorneal release and the in vivo IOP-lowering effects of Latanoprost ophthalmic gel formulations using Azone as a penetration enhancer and Carbopol-974® as a mucoadhesive.

The objective of this study was to maximize the in vitro transcorneal release, the intraocular pressure (IOP) lowering effect and the duration of action, of the Latanoprost acid (LAT) ophthalmic gels. The in vitro transcorneal release of LAT from a first set of gel formulations containing different concentrations of Azone (as enhancer) with a fixed concentration of C-974® (as mucoadhesive) was studied. The formulation that showed the greatest permeability at the lowest Azone concentration was selected for the preparation of a second set of ocular gels containing different C-974® concentrations. Their in vitro permeabilities were evaluated, and the C-974® concentration yielding the greatest in vitro permeability was chosen. The in vivo IOPlowering efficacy study for the scaled-up formulations from both sets of the test formulations was performed using a Tono-pen Avia® tonometer in rabbits for 4 consecutive days. To determine the duration of action, the most effective formulations were used for a single-dose study, and the IOP was measured at predetermined intervals until the IOP base-line was reestablished. The majority of the tested formulations showed significant but varied augmentations in both the in vitro and in vivo permeability results. The formulations GAZ-4 and GC-4 showed the greatest IOP lowering effects, i.e., 7.8±1.8 mmHg and 6.5±2.1 mm Hg, respectively. It is particularly noteworthy that for both formulations the IOP lowering effect continued for 24 hours. Their duration of action in the single-dose study were 47±2.25 hours and 48±1.5 hours, respectively. It was concluded that the in vitro release, onset, magnitude and duration of action of the LAT gels were increased and extended for up to 2 days for the two gel formulations

Real-Time Label-Free Targeting Assessment and in Vitro Characterization of Curcumin-Loaded Poly-lactic-co-glycolic Acid Nanoparticles for Oral Colon Targeting

The exploitation of curcumin for oral disease treatment is limited by its low solubility, poor bioavailability, and low stability. Surface-functionalized poly-lactic-co-glycolic acid (PLGA) nanoparticles (NPs) have shown promising results to ameliorate selective delivery of drugs to the gastro-intestinal tract. In this study, curcumin-loaded PLGA NPs (C-PLGA NPs) of about 200 nm were surface-coated with chitosan (CS) for gastro-intestinal mucosa adhesion, wheat germ agglutinin (WGA) for colon targeting or GE11 peptide for tumor colon targeting. Spectrometric and zeta potential analyses confirmed the successful functionalization of the C-PLGA NPs. Real-time label-free assessment of the cell membrane-NP interactions and NP cell uptake were performed by quartz crystal microbalance coupled with supported lipid bilayers and by surface plasmon resonance coupled with living cells. The study showed that CS-coated C-PLGA NPs interact with cells by the electrostatic mechanism, while both WGA- and GE11-coated C-PLGA NPs interact and are taken up by cells by specific active mechanisms. In vitro cell uptake studies corroborated the real-time label-free assessment by yielding a curcumin cell uptake of 7.3 ± 0.3, 13.5 ± 1.0, 27.3 ± 4.9, and 26.0 ± 1.3 μg per 104 HT-29 cells for noncoated, CS-, WGA-, and GE11-coated C-PLGA NPs, respectively. Finally, preliminary in vivo studies showed that the WGA-coated C-PLGA NPs efficiently accumulate in the colon after oral administration to healthy Balb/c mice. In summary, the WGA- and GE11-coated C-PLGA NPs displayed high potential for application as active targeted carriers for anticancer drug delivery to the colon.Peer reviewe

EFFECT OF PEGYLATED EDGE ACTIVATOR ON SPAN 60 BASED- NANOVESICLES: COMPARISON BETWEEN MYRJ 52 AND MYRJ 59

Objective: In recent years, Span 60 based nanovesicles have been the object of growing scientific attention as an alternative potential drug delivery system to conventional liposomes. Surface modification of nanovesicles can adjust the drug release rate and the affinity for the target site. The aim of present work was firstly to study the effects of different PEGylated edge activator (Myrj 52 and Myrj 59) on Span 60 based nanovesicles.Methods: Nanovesicles were prepared using Span 60 alone or in combination with Myrj 52 (polyethylene glycol 2000 monostearate) or Myrj 59 (polyethylene glycol 4400 monostearate) by employing the ethanol injection method. Myrj 52 and Myrj 59 are hydrophilic nonionic surfactants were used to modify the surface of the developed vesicles. Dynamic light scattering was used to determine the size, zeta potential and polydispersity index of the nanovesicles formulation. The vesicles were also characterized for entrapment efficiency and in vitro release.Results: In current work, the modified nanovesicles size (ranging from 54.32 to 141.7 nm), zeta potential (ranging from -5.67 to -27.1 mV) and polydispersity index (ranging from0.248 to 0.531) indicated that the surface modified nanovesicles vesicles are a homogenous and mono-disperse nanovesicles dispersions. The non-modified nanovesicles are showed higher particles size (>2 times) compared to modified nanovesicles. The modified nanovesicles were showed entrapment efficiency ranging from 36.42 to 78.13 %. All the modified nanovesicles showed accepted in vitro release of TN from nanovesicles (>70% released after 8 h), followed Higuchi models as drug release mechanism.Conclusion: In conclusion, these surface modified nanovesicles could be used as a potential drug carrier for a variety of drugs.                     Peer Review History: Received 16 July 2019;   Revised 12 August; Accepted 9 September, Available online 15 September 2019 Academic Editor: Prof. Dr. Gorkem Dulger, Duzce University, Turkey, [email protected] Received file:                Reviewer's Comments: Average Peer review marks at initial stage: 6.5/10 Average Peer review marks at publication stage: 9.5/10 Reviewer(s) detail: Dr. Robert Tungadi, State University of Gorontalo, Indonesia, [email protected] Prof. Dr. Kapil Kumar, Global Institute of Pharmaceutical Education and Research,Kashipur, US Nagar, Uttarakhand, India, [email protected] Similar Articles: SCREENING STUDY FOR FORMULATION VARIABLES IN PREPARATION AND CHARACTERIZATION OF CANDESARTAN CILEXETIL LOADED NANOSTRUCTURED LIPID CARRIER