明胶/海藻酸钠(京尼平交联)互穿网络膜的制备与性能

为了提高海藻酸钠与明胶各自的性能,首先,以海藻酸钠和明胶为原料,以京尼平、CaCl2为交联剂,采用分步交联法制备了明胶/海藻酸钠互穿网络膜。然后,利用FTIR对明胶/海藻酸钠互穿网络结构进行了表征与分析,根据FTIR结果推测了互穿网络结构形成的机制。最后,探讨了京尼平的加入量和明胶与京尼平的质量比对互穿网络膜力学性能和交联度的影响,及海藻酸钠与明胶的质量比对互穿网络膜力学性能、断面形貌、热稳定性和吸水保水性能的影响。结果表明:当明胶与京尼平的质量比为200∶1、海藻酸钠与明胶的质量比为2∶1时,互穿网络膜具有最佳的力学性能、吸水保水性能和相容性;此外,互穿网络膜的力学性能也优于纯海藻酸钠膜与纯明胶膜的。明胶的加入提高了互穿网络膜在低温区的热稳定性,但降低了高温区的热稳定性。海藻酸钠与明胶之间可能以分子间作用力、氢键及离子键等相互作用,提高了二者各自的初始分解温度与最大热分解温度。研究解决了海藻酸钠与明胶力学性能差的问题,为拓展海藻酸钠在医用领域的应用提供参考。     

Nanosuspension of efavirenz for improved oral bioavailability: formulation optimization,in vitro,in situ and in vivo evaluation

Context: Nanosuspensions (NSs) of poorly water-soluble drugs are known to increase the oral bioavailability.

Objectives: The purpose of this study was to develop NS of efavirenz (EFV) and to investigate its potential in enhancing the oral bioavailability of EFV.

Materials and methods: EFV NS was prepared using the media milling technique. The Box–Behnken design was used for optimization of the factors affecting EFV NS. Sodium lauryl sulfate and PVP K30 were used to stabilize the NS. Freeze-dried NS was completely re-dispersed with double-distilled filtered water.

Results: Mean particle size and zeta potential of the optimized NS were found to be 320.4?±?3.62?nm and –32.8?±?0.4 mV, respectively. X-ray diffraction and differential scanning calorimetric analysis indicated no phase transitions. Rate and extent of drug dissolution in the dissolution medium for NS was significantly higher compared to marketed formulation. The parallel artificial membrane permeability assay revealed that NS successfully enhanced the permeation of EFV. Results of in situ absorption studies showed a significant difference in absorption parameters such as K_a, t_1/2 and uptake percentages between lyophilized NS and marketed formulation of EFV. Oral bioavailability of EFV in rabbits resulting from NS was increased by 2.19-fold compared to the marketed formulation.

Conclusion: Thus, it can be concluded that NS formulation of EFV can provide improved oral bioavailability due to enhanced solubility, dissolution velocity, permeability and hence absorption.     

Design and optimization of thermosensitive nanoemulsion hydrogel for sustained-release of praziquantel

Objective: This work aimed to develop an alternative sustained-release thermosensitive praziquantel-loaded nanoemulsion (PZQ-NE) hydrogel for better schistosomiasis treatment.

Significance: PZQ-NE-dispersed chitosan/glycerol 2-phosphate disodium/HPMC (NE/CS/β-GP/HMPC) hydrogel was successfully prepared to improve bioavailability of PZQ.

Methods: Solubility tests and pseudo-ternary phase diagrams were applied to screen optimal oils, surfactants and co-surfactants of NE. The hydrogels were characterized for gelling time, surface exudates, rheological properties and in vitro drug release. Formulation optimization of NE/CS/β-GP/HMPC hydrogel was conducted by Box–Behnken experimental design combined with response surface methodology. In vitro cytotoxicity of hydrogel was studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide method. The sustained-release property of PZQ in NE and optimized hydrogel was evaluated by pharmacokinetic study in rabbits.

Results: The formulation of PZQ-NE consisted of mass ratio of 12.5% capryol 90 containing PZQ (160?mg/g), 40% cremophor RH 40/tween 20 and transcutol HP (S/CoS?=?2:1), 47.5% deionized water. PZQ releasing from NE/CS/β-GP/HMPC hydrogels was best fitted to Higuchi model and governed by diffusion. Rheological investigation evidenced the themosensitive gelation of different hydrogel systems and their gel-like character at 37?°C. The optimized hydrogel formulation consisted of HPMC solution (103.69?mg/g), 3.03% (w/v) chitosan and 14.1% (w/v) β-GP showed no cytotoxicity when the addition of NE was no more than 100?mg/g. Pharmacokinetic parameters indicated that NE/CS/β-GP/HMPC hydrogel can significantly slow down drug elimination, prolong mean residence time and improve bioavailability of PZQ.

Conclusions: NE/CS/β-GP/HMPC hydrogel possessed sustained-release property and could be an alternative antischistosomal drug delivery system with improved therapeutic effect.     

Preparation and optimization of a novel microbead formulation to improve solubility and stability of curcumin

Curcumin is an active ingredient which is poorly water-soluble, leading to a low oral bioavailability. The aim of this research was to prepare a novel microbead formulation, and to solubilize, solidify, and improve storage stability of curcumin. Firstly, curcumin was solubilized with Kolliphor^TM RH40 and then microencapsulated by cross linking of sodium alginate with calcium chloride. A three-factor, three-level Box–Behnken design was employed to acquire the optimum microbead formulation, namely the best entrapment efficiency and in vitro curcumin release. The independent variables were sodium alginate concentration, calcium chloride concentration, and the weight of curcumin solution, while the dependent variables were entrapment efficiency and in vitro curcumin release. The optimized microbead formulation was 2.06% sodium alginate, 24.33% calcium chloride, and 1.28 g curcumin solution (containing curcumin and RH40 with a ratio of 1:22, g/g). Results showed that high concentrations of sodium alginate and calcium chloride could increase the entrapment efficiency. In vitro curcumin release decreased with increasing of sodium alginate as well as decreasing of calcium chloride. In conclusion, the optimum microbead formulation increased the solubility of curcumin and enhanced its stability, and achieved a high entrapment efficiency and in vitro curcumin release.     

Formulation,optimization, hemocompatibility and pharmacokinetic evaluation of PLGA nanoparticles containing paclitaxel

Objective: Paclitaxel (PTX)-loaded polymer (Poly(lactic-co-glycolic acid), PLGA)-based nanoformulation was developed with the objective of formulating cremophor EL-free nanoformulation intended for intravenous use.

Significance: The polymeric PTX nanoparticles free from the cremophor EL will help in eliminating the shortcomings of the existing delivery system as cremophor EL causes serious allergic reactions to the subjects after intravenous use.

Methods and results: Paclitaxel-loaded nanoparticles were formulated by nanoprecipitation method. The diminutive nanoparticles (143.2?nm) with uniform size throughout (polydispersity index, 0.115) and high entrapment efficiency (95.34%) were obtained by employing the Box–Behnken design for the optimization of the formulation with the aid of desirability approach-based numerical optimization technique. Optimized levels for each factor viz. polymer concentration (X1), amount of organic solvent (X2), and surfactant concentration (X3) were 0.23%, 5?ml %, and 1.13%, respectively. The results of the hemocompatibility studies confirmed the safety of PLGA-based nanoparticles for intravenous administration. Pharmacokinetic evaluations confirmed the longer retention of PTX in systemic circulation.

Conclusion: In a nutshell, the developed polymeric nanoparticle formulation of PTX precludes the inadequacy of existing PTX formulation and can be considered as superior alternative carrier system of the same.     

高压缩强度聚丙烯酸盐/聚硅氧烷互穿网络水凝胶的制备

利用γ-(2,3-环氧丙氧)丙基三甲氧基硅烷(KH-560)的水解和缩聚,将其引入聚丙烯酸盐水溶液中,以N,N'-亚甲基双丙烯酰胺为交联剂,过硫酸铵为引发剂采用水溶液聚合法合成出具有较高压缩强度的新型聚丙烯酸盐/聚硅氧烷互穿网络聚合物.压缩实验表明,压缩强度受KH-560用量,水凝胶溶胀率及交联密度的影响.由于含有离子性基团,该新型水凝胶具有pH敏感性.     

Synthesis of polyacrylate/polyethylene glycol interpenetrating network hydrogel and its sorption of heavy-metal ions

Abstract

A simple two-step aqueous polymerization method was introduced to synthesize a polyacrylate/polyethylene glycol (PAC/PEG) interpenetrating network (IPN) hydrogel. On the basis of the effects of the ratio of PAC to PEG, neutralization degree, heavy-metal ion concentration, and temperature on the adsorption behavior of PAC/PEG IPN hydrogel toward Ni^{2 +}, Cr^{3 +} and Cd^{2 +}, the preparation conditions were optimized. In our system, the greatest amount of Ni^{2 +}, Cr^{3 +} and Cd^{2 +} adsorbed were 102.34, 49.38 and 33.41 mg g^{- 1}, respectively. The adsorption abilities of a dried PAC/PEG composite and a swollen PAC/PEG IPN hydrogel were compared. It was found that the efficiency of removing metal ions using the swollen hydrogel was greater than that using the dried composite. The adsorption mechanism and model are also discussed.     

Synthesis of polyacrylate/polyethylene glycol interpenetrating network hydrogel and its sorption of heavy-metal ions

A simple two-step aqueous polymerization method was introduced to synthesize a polyacrylate/polyethylene glycol (PAC/PEG) interpenetrating network (IPN) hydrogel. On the basis of the effects of the ratio of PAC to PEG, neutralization degree, heavy-metal ion concentration, and temperature on the adsorption behavior of PAC/PEG IPN hydrogel toward Ni^{2 +}, Cr^{3 +} and Cd^{2 +}, the preparation conditions were optimized. In our system, the greatest amount of Ni^{2 +}, Cr^{3 +} and Cd^{2 +} adsorbed were 102.34, 49.38 and 33.41 mg g^{- 1}, respectively. The adsorption abilities of a dried PAC/PEG composite and a swollen PAC/PEG IPN hydrogel were compared. It was found that the efficiency of removing metal ions using the swollen hydrogel was greater than that using the dried composite. The adsorption mechanism and model are also discussed.     

Implementation of two different experimental designs for screening and optimization of process parameters for metformin-loaded carboxymethyl chitosan formulation

Abstract

Metformin (MET) was effectively encapsulated into O-carboxymethyl chitosan (O-CMC) polymeric formulation using an experimental design method. Six factors Plackett–Burman (PB) design was utilized to find the significant process parameters. Linear equations used to study the effect of each process parameters on particle size (PS), encapsulation efficiency (EE), and zeta potential (ZP) and the most influential three factors decided for further optimization. Optimization was carried out by implementing three-factor three-level Box–Behnken (BB) design. Mathematical models were generated by regression analysis for responses of PS, EE, and ZP. Two-step experimental design took into account for the preparation of optimized formulation with maximum %EE (72.78?±?9.7%) and minimum PS (225.67?±?5.53?nm) at optimum process conditions with a ZP of –5.22?mV for the nano-polymeric formulation in an economical matter by reduction chemical use and formulation time. Furthermore, the biological activity of the final formulation was determined by in vitro cytotoxicity study compared to free MET. The cytotoxicity result reveals that both pure drug and nano-formulation biocompatible with MCF10A non-tumorigenic cell line and lethal for the MCF7 cell line. These in vitro results were the first helpful step to further investigate O-CMC loaded MET nanoparticles in diagnostic and therapeutic applications of breast cancer.     

细菌纤维素/聚乳酸互穿网络复合材料的结晶与熔融

为了研究细菌纤维素(BC)网络结构对聚乳酸(PLA)结晶与熔融过程的影响,以PLA为基体,BC为增强体,通过PLA-三氯甲烷溶液与BC-无水乙醇分散液的共混扩散制备了具有互穿网络结构的BC/PLA生物复合材料。采用SEM、偏光显微镜(POM)、DSC和莫志深(MO)模型研究了复合材料的微观形态、球晶形貌、非等温结晶动力学和熔融行为。结果表明:采用溶液共混扩散法可得到以BC为骨架、PLA缠绕其表面的互穿网络结构的复合材料。随降温速率增加,BC/PLA复合材料的结晶温度、熔融温度和相对结晶度均下降。BC可作为异相成核剂,适量添加可同时提高BC/PLA复合材料的结晶速率和相对结晶度,细化球晶尺寸。MO模型可较好地描述BC/PLA复合材料的非等温结晶动力学行为。     

Taste masking of azithromycin by resin complex and sustained release through interpenetrating polymer network with functionalized biopolymers

Abstract

Objective: The objective was to evaluate taste masking of azithromycin (AZI) by ion exchange resins (IERs) and the formation of covalent semi interpenetrating polymer network (IPN) beads using chitosan (CS) and sodium carboxylated agarose (SCAG) for sustained release of drug.

Methods: Methacrylic acid (MAA)-based IERs were prepared by suspension polymerization method. Drug release complexes (DRCs) were prepared by different drug:resin ratios i.e. 1:1, 1:2 and 1:4. The resultant DRCs were characterized using DSC, FTIR, PXRD, in vivo and in vitro taste masking, and in vitro drug release at gastric pH. IPN beads were prepared by entrapping DRCs with bio polymers and cross linked with trisodium citrate (NaCIT), and further cross-linked with glutaraldehyde (GA) for sustained release of AZI.

Results: In vitro and in vivo taste masking studies showed that MD1:4 DRC formulation was optimal. The release of AZI from DRC was found to be very fast at gastric pH i.e. 97.37?±?1.02% within 45?min. The formation of IPN beads was confirmed by FTIR. The release of drug from IPN beads at gastric and intestinal pH was found to be “<28% and <60%”, respectively. The release kinetics showed Fickian diffusion profile for ionically cross-linked beads and zero-order release mechanism for GA cross-linking beads.

Conclusions: DRCs can be effectively used for taste masking and newly formulated IPN beads demonstrated sustained release of AZI.     

Brain targeting of chitosan-based diazepam mucoadhesive microemulsions via nasal route: formulation optimization,characterization, pharmacokinetic and pharmacodynamic evaluation

Objective: The aim of present investigation was to develop microemulsions (MEs) and mucoadhesive microemulsions (MME) of diazepam for brain uptake through nasal administration for the treatment of seizure emergency.

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.     

Process,optimization, and characterization of budesonide-loaded nanostructured lipid carriers for the treatment of inflammatory bowel disease

The major challenge involved in the treatment of inflammatory bowel disease is targeted delivery of the drug at the site of inflammation. As nanoparticles possess the ability to accumulate at the site of inflammation, present investigation aims at development of Budesonide-loaded nanostructured lipid carrier systems (BDS-NLCs) for the treatment of inflammatory bowel disease. BDS-NLCs were prepared by employing a high pressure homogenization technique. Various preliminary trials were performed for optimization of the NLCs in which different processes, as well as formulation parameters, were studied. The BDS-NLCs was optimized statistically by applying a 3-factor/3-level Box–Behnken design. Drug concentration, surfactant concentration, and emulsifier concentration were selected as independent variables, and % entrapment efficiency and particle size were selected as dependent variables. The best batch comprises of 10%, 7%, and 20% w/w concentration of drug, surfactant, and emulsifier, respectively, with % entrapment efficiency of 92.66?±?3.42% and particle size of 284.0?±?4.53?nm. Further, in order to achieve effective delivery of nanoparticulate system to colonic region, the developed BDS-NLCs were encapsulated in Eudragit^® S100-coated pellets. The drug release studies of pellets depict intactness of BDS-NLCs during palletization process, with f₂ value of 75.879. The in vitro evaluation of enteric-coated pellets revealed that a coating level of 15% weight gain is needed in order to impart lag time of 5?h (transit time to reach colon). The results of the study demonstrate that the developed BDS-NLCs could be used as a promising tool for the treatment of inflammatory bowel disease.     

Nanostructured lipid carriers engineered for intranasal delivery of teriflunomide in multiple sclerosis: optimization and in vivo studies

Background: Multiple sclerosis (MS) is one of the most severe autoimmune disorder of the central nervous system (CNS).

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 J_ss 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.     

温度敏感聚丙烯酸盐/聚乙二醇互穿网络水凝胶的合成及重金属离子吸收

以N,N'-亚甲基双丙烯酰胺为交联剂,过硫酸铵为引发剂采用新型两步水溶液聚合法合成出聚丙烯酸盐/聚乙二醇互穿网络(PAA/PEG IPN)水凝胶.对其溶胀性能进行了研究,结果表明,该水凝胶具有正温度敏感性,其LCST为25℃.基于聚丙烯酸盐与金属阳离子的络合作用,将该水凝胶用于重金属离子的回收.采用SEM、FTIR对其结构及表面形貌进行表征.     

Formulation,optimization, and characterization of rifampicin-loaded solid lipid nanoparticles for the treatment of tuberculosis

Abstract

Mycobacterium tuberculosis, being the causative infectious agent, is the leading cause of death worldwide amongst the infectious disease. The low bioavailability of rifampicin (RIF), one of the vital constituent of antitubercular therapy, instigates an urge to develop nanocarrier, which can prevent its degradation in the acidic pH of the stomach. Solid lipid nanoparticles (SLNs) have been proven to be promising versatile platform for oral delivery of lipophilic drugs. Therefore, the current investigation demonstrates development of RIF-loaded solid lipid nanoparticles (RIF-SLNs) using high-pressure homogenization technique by employing a three-level, three-factor Box–Behnken design. Concentration of drug, concentration of emulsifier, and homogenization pressure were selected as an independent variables, and %drug loading (%DL), %entrapment efficiency (%EE), and particle size were selected as dependent variables. The developed RIF-SLNs were characterized for particle size, polydispersity index, zeta potential, %EE, %DL, differential scanning calorimetry, X-ray diffraction, and TEM analysis. The mean diameter of RIF-SLNs was found to be 456?±?11?nm, %EE of 84.12?±?2.78%, and %DL of 15.68?±?1.52%. The in vitro lipolysis experiments revealed that RIF-SLNs stabilized using poloxamer 188, exhibited antilipolytic effect. Furthermore, the in vitro GI stability studies (at pH 1.2, pH 4.5, pH 6.8, and pH 7.4) revealed that the developed system could withstand various gastrointestinal tract media. The in vitro dissolution studies depicted biphasic drug release profile for drug-loaded SLNs revealing best fit with Weibull model. The accelerated stability studies for 6?months does not revealed any significant change in characteristics of developed RIF-SLNs.     

Beneficiation of low-grade iron ore fines by multi-gravity separator (MGS) using optimization studies

There is an urgent need for development of environmental friendly processes through which iron ore fines can be beneficiated and utilized effectively. For processing of low-grade iron ores, ground to finer size necessitates the use of centrifugal force. This is because the settling rate of the particles in centrifugal force is 500–600 times more than that noticed for the nominal gravitational force. Multi-gravity separator (MGS) is the one such unit used for recovering hematitic fines without addition of chemicals. In the present article, an approach has been made to beneficiate low-grade hematitic iron ore of Jilling mine, Odisha, India, using MGS. The effect of three important variables was studied and their influences were analyzed through statistical approach to optimize grade, recovery, and separation efficiency. Use of response surface methodology (RSM) based on Box–Behnken design has also been adopted for analysis purpose. The results obtained indicate that it is possible to beneficiate low-grade hematitic iron ore from a feed of 50.74% Fe to 65.11% Fe with an acceptable recovery of 71.88%. Optimization of process variables was done for each response, optimized independently irrespective of other responses. Further optimization of the variables was carried out with a multi-objective target.     

A combination of complexation and self-nanoemulsifying drug delivery system for enhancing oral bioavailability and anticancer efficacy of curcumin

Abstract

Objective: Curcumin, the golden spice from Indian saffron, has shown chemoprotective action against many types of cancer including breast cancer. However, poor oral bioavailability is the major hurdle in its clinical application. In the recent years, self-nanoemulsifying drug delivery system (SNEDDS) has emerged as a promising tool to improve the oral absorption and enhancing the bioavailability of poorly water-soluble drugs. In this context, complexation with lipid carriers like phospholipid has also shown the tremendous potential to improve the solubility and therapeutic efficacy of certain drugs with poor oral bioavailability.

Methods: In the present investigation, a systematic combination of both the approaches is utilized to prepare the phospholipid complex of curcumin and facilitate its incorporation into SNEDDS. The combined use of both the approaches has been explored for the first time to enhance the oral bioavailability and in turn increase the anticancer activity of curcumin.

Results: As evident from the pharmacokinetic studies and in situ single pass intestinal perfusion studies in Sprague–Dawley rats, the optimized SNEDDS of curcumin–phospholipid complex has shown enhanced oral absorption and bioavailability of curcumin. The cytotoxicity study in metastatic breast carcinoma cell line has shown the enhancement of cytotoxic action by 38.7%. The primary tumor growth reduction by 58.9% as compared with the control group in 4T1 tumor-bearing BALB/c mice further supported the theory of enhancement of anticancer activity of curcumin in SNEDDS.

Conclusion: The developed formulation can be a potential and safe carrier for the oral delivery of curcumin.     

Optimization of reagent dosages with the use of response surface methodology and evaluation of test results with upgrading curves in graphite flotation

The aim of this study is to reduce reagent consumptions in graphite flotation with the addition of Aero 3477 promoter to the flotation stage. A three-level Box–Behnken design is used for optimization and modeling of flotation stages. For this purpose, the flotation experiments are performed in two steps. The maximum weight recovery and the minimum ash content values of the rougher concentrate are calculated as 21.41 and 32.49% using diesel oil dosage (714.24?g/t), methyl isobutyl carbinol (MIBC) dosage (212.81?g/t), and sodium silicate (Na₂SiO₃) dosage (1451.189?g/t), respectively, in the preliminary experiment tests. Subsequently, keeping the Na₂SiO₃ dosage constant, Aero 3477 promoter is added to the flotation stage to provide reduction at reagent consumptions. As a result, the reagent consumptions of diesel oil dosage (162.10?g/t), MIBC dosage (129.58?g/t), and Aero 3477 promoter dosage (168.96?g/t) are supplied to reach the approximate weight recovery and the ash content as in primary experimental results. Considerable dosage decreases in both diesel oil and MIBC are achieved using promoter. Moreover, experimental studies are also evaluated using upgrading curves.