Rachmat Mauludin

Curcumin nanoemulsion for transdermal application: formulation and evaluation

Abstract The aim of this work is to develop a curcumin nanoemulsion for transdermal delivery. The incorporation of curcumin inside a nanoglobul should improve curcumin stability and permeability. A nanoemulsion was prepared by the self-nanoemulsification method, using an oil phase of glyceryl monooleate, Cremophor RH40 and polyethylene glycol 400. Evaluation of the nanoemulsion included analysis of particle size, polydispersity index, zeta potential, physical stability, Raman spectrum and morphology. In addition, the physical performance of the nanoemulsion in Viscolam AT 100P gel was studied. A modified vertical diffusion cell and shed snake skin of Python reticulatus were used to study the in vitro permeation of curcumin. A spontaneously formed stable nanoemulsion has a loading capacity of 350 mg curcumin/10 g of oil phase. The mean droplet diameter, polydispersity index and zeta potential of optimized nanoemulsion were 85.0 ± 1.5 nm, 0.18 ± 0.0 and −5.9 ± 0.3 mV, respectively. Curcumin in a nanoemulsion was more stable than unencapsulated curcumin. Furthermore, nanoemulsification significantly improved the permeation flux of curcumin from the hydrophilic matrix gel; the release kinetic of curcumin changed from zero order to a Higuchi release profile. Overall, the developed nanoemulsion system not only improved curcumin permeability but also protected the curcumin from chemical degradation.

Improving mechanical properties of desloratadine via multicomponent crystal formation

ABSTRACT We report the first multicomponent crystal of desloratadine, an important anti‐histamine drug, with a pharmaceutically acceptable coformer of benzoic acid. The single crystal structure analysis revealed that this novel multicomponent crystal is categorized as salt due to the proton transfer from benzoic acid to the desloratadine molecule. By forming the salt multicomponent crystal, we demonstrated that the tabletability and plasticity of the multicomponent crystal was improved from the parent drug. In addition, neither capping nor lamination tendency was observed in the desloratadine‐benzoic acid multicomponent crystal. The existence of a layered structure and slip planes are proposed to be associated with this improvement. The desloratadine‐benzoate in this case shows an improved solubility in water and HCl 0.1N media and a better dissolution profile in water. However, the dissolution rate in HCl 0.1N media was found to be essentially indifference. Graphical abstract Figure. No Caption available.

HYDRATE TRANSFORMATION STUDY OF FLUOROQUINOLONE ANTIBIOTICS USING FOURIER TRANSFORM INFRARED SPECTROSCOPY (FTIR)

Objective: There are many successful products on the market which are the culmination of the self-micro-emulsification lipid technology applications. Despite the importance of lipid-based formulations, these systems have some limitations including; stability, complexity during large scale manufacturing process and limited dosage forms to such as soft gelatin capsule. In order to overcome these limitations, the prospect of converting self-micro-emulsifying drug delivery systems (SMEDDS) into tablet dosage form was investigated in this study. Methods: A self-micro-emulsifying oil formulation representing type III A lipid class composed of glycerox 767HC/croduret 40 ss at ratios of (80/20) was converted into solid SMEDDS using solid carrier adsorption method. Powder blends containing magnesium trisilicate hydrate (MTSH) or magnesium lluminum silicate (MAS) at various oil loading factors were mixed with MCC with and without various binders and compressed into tablets using a fixed loading force of approximately of 5 KN. Hardness profiles of these oil loaded tablets were then analyzed. Results: Powder compacts which contained MTSH with and without SMEDDS oil had shown relatively better compaction properties than MAS. Adding SMEDDS oil solution to either MTSH or MAS at ratios of 1:9 has relatively reduced tablets hardness by almost 2 or 4 folds, respectively. Conclusion: Progressive inclusion of increasing amounts of SMEDDS oil solution adsorbed unto the solid carrier has incurred a further reduction in the hardness of SMEDDS tablets. It appears that manufacturing of tablet SMEDDS can only be attainable for highly potent drugs as minimal amounts of oil solution added to the powder blends can adversely affect the mechanical strength of compressed tablet.

Synthesis, characterization, and stability study of desloratadine multicomponent crystal formation

This study describes the formation of multicomponent crystal (MCC) of desloratadine (DES). The objective of this study was to discover the new pharmaceutical MCC of DES using several coformers. The MCC synthesis was performed between DES and 26 coformers using an equimolar ratio with a solvent evaporation technique. The selection of the appropriate solvent was carried out using 12 solvents. The preview of the MCC of DES was performed using polarized light microscopy (PLM). The formation of MCC was confirmed using powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). The accelerated stability of MCC at 40 °C and relative humidity of 75% was investigated using PXRD and FTIR. Depending on the prior evaluation, DES and benzoic acid (BA) formed the MCC. PLM and SEM results showed that crystal habit of combination between DES and BA differed from the constituent components. Moreover, the diffractogram pattern of DES-BA was distinct from the constituent components. The DSC thermogram showed a new peak which was distinct from both constituent components. The FTIR study proved a new spectrum. All characterizations indicated that a new solid crystal was formed, ensuring the MCC formation. In addition, DES-BA MCC had both chemical and physical stabilities for a period of 4 months.

A Novel Desloratadine-Benzoic Acid Co-Amorphous Solid: Preparation, Characterization, and Stability Evaluation

Low physical stability is the limitation of the widespread use of amorphous drugs. The co-amorphous drug system is a new and emerging method for preparing a stable amorphous form. Co-amorphous is a single-phase amorphous multicomponent system consisting of two or more small molecules that are a combination of drugs or drugs and excipients. The co-amorphous system that uses benzoic acid (BA) as an excipient was studied to improve the physical stability, dissolution, and solubility of desloratadine (DES). In this study, the co-amorphous formation of DES and BA (DES–BA) was prepared by melt-quenching method and characterized by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD), and polarized light microscopy (PLM). Dissolution, solubility, and physical stability profiles of DES–BA were determined. The DES crystals were converted into DES–BA co-amorphous form to reveal the molecular interactions between DES and BA. Solid-state analysis proved that the co-amorphous DES–BA system (1:1) is amorphous and homogeneous. The DSC experiment showed that the glass transition temperature (Tg) of tested DES–BA co-amorphous had a higher single Tg compared to the amorphous DES. FTIR revealed strong interactions, especially salt formation. The dissolution rate and solubility of co-amorphous DES–BA (1:1) obtained were larger than the DES in crystalline form. The PXRD technique was used to assess physical stability for three months at 40 °C with 75% RH. The DES–BA co-amorphous system demonstrated better physical stability than a single form of amorphous DES. Co-amorphous DES–BA has demonstrated the potential for improving solid-state stability, as the formation of DES–BA co-amorphous salt increased solubility and dissolution when compared to pure crystalline DES. This study also demonstrated the possibility for developing a DES–BA co-amorphous system toward oral formulations to improve DES solubility and bioavailability.

PVA-Ketoprofen Nanofibers Manufacturing Using Electrospinning Method for Dissolution Improvement of Ketoprofen

Background and purpose: Ketoprofen is an NSAIDs agent which has analgesic and anti inflammation effects. Ketoprofen is classified into class II in the biopharmaceutical classification system that has a high permeability but low solubility. Hence, the absorption rate of this substance is governed by its dissolution rate. Electrospinning is a method that combine solid dispersion technology and nanotechnology. This method can be selected to enhance the dissolution rate of active substances. The aim of this research is to improve the dissolution rate of ketoprofen through the preparation of polymeric nanofiber polivinyl alcohol (PVA) containing ketoprofen using electrospinning process. Methods: Preparation of nanofibers with various of PVA-ketoprofen ratio, flow rate, and PVA concentration in the solution were accomplished using electrospinning instrument. Casting solid dispersion film were also prepared by solvent evaporation method and used as a reference. The rates of dissolution of ketoprofen from each of nanofibers, casting films, and pure ketoprofen were conducted in HCl pH 1.2 medium at 37oC. Characterization of nanofibers was carried out using Scanning Electron Microscope (SEM) and X-ray Diffraction (XRD). Results: Nanofibers which contained of PVA-ketoprofen 1:1 in ratio w/w showed a significant improvement in dissolution (p<0.05) compared to the pure ketoprofen. Meanwhile, nanofibers obtained from a solution containing 7.5 % PVA (w/v) and 4 ml/h in flow rate showed the best dissolution rate improvement and significantly different (p<0.05) with either the casting film or the pure ketoprofen. The improvement of ketoprofen dissolution was due to the increasing of surface area of nanofiber and the change of ketoprofen from crystalline into amorphous form. Conclusion: Electrospinning technique can be used to improve the dissolution rate of ketoprofen through the PVA-ketoprofen nanofiber formation by choosing the appropriate polymer concentration and manufacturing process.

Influence of mechanical and thermal energy on rifampicin

The same raw material has opportunity to show different physical properties if it is produced by different industries. For such reason, rifampicin was chosen as a raw materials model, thats obtaining from five resource countries and were obtained from five different suppliers, each coded A, B, C, D and E. Each raw material was handled under tribomechanic and thermal treatment. Mechanical treatment was carried out by using grinding mill at 100 rpm for 30 minutes. Thermal treatment was carried out by oven at 105oC for 2 hours. Transformation occured, was identified by differential scanning calorymetry (DSC), X-ray powder diffraction and dissolution rate. The intrinsic dissolution rate was determined in 900 mL HCl 0,1N oxygen free, using basket and calculated through simultaneously determination method using uv spectrophotometry at λabs.maks. 475 nm. Thermograms of five milled raw material showed endothermic curve at 58oC without obviously melting curve. Thermogram of heated raw material did not show endothermic curve except its melting at 188oC-192oC. Crystallinity indices of the raw materials decreased from C, E, B, A to D. The milled raw materials were mixture of rifampicin II (2%) and amorphous (98%). A and D were mixture of rifampicin form II and fines (amorph). The other samples were only rifampicin form II. All of the raw materials showed different dissolution rates. Rifampicin B,C and D had sameness dissolution rate, whether milled or heated. Key words : Rifampicin II, rifampicin amorphous, DSC, powder X-ray diffraction, dissolution rate