Development and Characterisation of Tetrahydrocurcumin-Loaded Lipid-Polymer Hybrid Nanoparticles to Enhance its Oral Bioavailability Paper16
The development of new drugs alone is not sufficient to ensure progress in drug therapy. Several drugs with oral administration have poor solubility, poor absorption, rapid metabolism, elimination, and high fluctuation of plasma levels, and hence unpredictable and poor bioavailability. A promising strategy to overcome these problems involves the development of suitable drug carrier systems using nanoparticles (NPs). Tetrahydrocurcumin (THC) is an active metabolite of curcumin, which comes under BCS Class IV. Less solubility and permeability of the active agents led the way to the BCS classification IV. A novel, integrated system known as lipid-polymer hybrid nanoparticles (LPH-NPs) has been introduced in an effort to mitigate limitations associated with unpredictable physicochemical properties. The particle size, zeta potential, encapsulation efficiency and morphology were characterized for the prepared formulation. In-vitro drug release kinetics and stability of the prepared LPH-NPs were evaluated. Solubility parameters were analysed to predict the final formulation development. The drug release from the formulation was clearly indicative of sustained release of THC. The developed formulation showed good stability during storage.
QUALITY BY DESIGN (QbD) ASSISTED DEVELOPMENT OF SPONGE DRESSING CONTAINING NANOCURCUMIN AND LACTOBACILLUS PLANTARUM (L-CLEN) FOR INFECTIOUS WOUNDS
Joga Singha*,Simarjot Kaur Sandhua, Jayant Rauta, Suneel Kumarb, Mandeep Singha, Vikas Ranac, Praveen Rishid, N. Ganeshe, Indu Pal Kaura#
a-University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh
b-Department of Biomedical Engineering, Rutgers, The State University of New Jersey, Piscataway, New Jersey.
c-Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala
d-Department of Microbiology, Panjab University, Chandigarh, India
e-Jawaharlal Nehru cancer Hospital & Research Centre, Bhopal India
Dr Indu Pal Kaur, Chairperson and Professor of Pharmaceutics, University Institute of Pharmaceutical Sciences Panjab University, Chandigarh 160014, India
Present study endeavoured to explore synergistic effect of solubilised, stabilised, slow releasing nanocurcumin (solid lipid nanoparticles; CSLNs) and a probiotic, Lactobacillus plantarum UBLP-40 (L-CLEN) combination for wound healing. Combination showed 560% enhanced antimicrobial effects against planktonic and biofilms of skin pathogen, Staphylococcus aureus 9144. Sterile sponge wound dressing (L-CLEN) incorporating probiotic, alginate and gelatinin CSLNs dispersion was designed and optimised using central composite design (201811044487; PCT/IB2019/060162). FESEM revealed that Lactobacillus plantarum and CSLNs were embedded within polymeric meshwork of the sponge. L-CLEN degraded and released Lactobacillus plantarum, which germinated in the wound bed. Sponge was stable under refrigerated conditions for six months. Safety was confirmed in terms of translocation of probiotic from wound to internal organs. The dressing exhibited faster wound closure; decrease in bioburden, TNF-α, MMP-9 and LPO levels; and increase in VEGF, TGF-β and antioxidant enzymes (catalase, GSH) in comparison to CSLNs and probiotic alone dressings confirming a synergistic effect on multiple healing processes.
FORMULATION AND EVALUATION OF CYCLODEXTRIN BASED NANOSPONGES FOR DISSOLUTION IMPROVEMENT OF CILOSTAZOL
Mayuri Jadav*, Ashok Neelkanth Mahajan
Department of Pharmaceutics, Babaria Institute of Pharmacy, BITS Edu Campus, Vadodara- Mumbai NH-8, Varnama, Vadodara-391240, Gujarat, India
Cilostazol (CZ) is an antiplatelet agent approved by USFDA. However incomplete absorption of CZ from tablets in human is due to its poor water solubility. Hence the objective of present investigation was to synthesize, characterize the cyclodextrin (BCD) based nanosponges(NS) and to improve the solubility and dissolution characteristics of CZ by formulating into cyclodextrin based NS. NS were prepared by ultrasound assisted synthesis method. CZ loaded NS were characterized by FTIR, X-ray diffraction, DSC and SEM, phase solubility and solution interaction studies. Phase solubility studies confirmed the enhanced solubilization ability of NS over the plain beta cyclodextrin molecule. The solution state interaction studies, FTIR, DSC and X-ray diffraction studies confirmed the formation of an inclusion complex between CZ & NS. CZ loaded NS formulation having the ratio of 1:3 showed 90% drug release in 60 minutes as compared to plain CZ powder. This study concluded that cyclodextrin based nanosponges can be an effective method to improve the dissolution characteristic of poorly soluble BCS class II drug CZ.
A SIMPLE, SCALABLE IN SITU TECHNIQUE FOR AMPHOTERICIN B SOLID LIPID NANOPARTICLE PREPARATION WITH HIGH SAFETY AND EFFICACY
Saugandha Das* and Padma V. Devarajan
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Deemed University, Elite Status and Centre of Excellence (Maharashtra), N.P. Marg, Matunga (E), Mumbai, 400019, Maharashtra, India
Amphotericin B (AmB) is a drug of choice for severe systemic fungal and parasitic infections like Visceral Leishmaniasis (VL), but is challenged by severe kidney toxicity. Although liposomal formulations have addressed toxicity issues of AmB, high cost, stability and scale up challenges restrict clinical usage. In this study we exploited a simple and revolutionary, in-house, In situ approach for the design of solid lipid nanoparticles of AmB (IsAmBSLN), which could bypass the scale up challenges associated with conventional nanocarrier preparation. The method involves adding a drug preconcentrate to an aqueous medium to generate drug loaded nanocarriers of desired size and physiochemical properties. AmB preconcentrate was prepared simply by dissolving AmB, lipid and other excipients in a pharmaceutically approved vehicle and sterilized by membrane filtration. Just prior to use, the sterile preconcentrate was added to 5% dextrose solution and mixed to instantaneously form ready to inject, IsAmBSLN. Optimization was carried out by three level Box-Behnken design to obtain average PS ~250 nm and %EE >95% with high reproducibility. The AmB preconcentrate showed drug content >95% till 12 months when stored at refrigerated temperatures with no change in PS and %EE of IsAmBSLN. IsAmBSLN revealed negligible erythrocyte and macrophage toxicity and 4.62-fold higher efficacy against macrophage internalized Leishmania amastigotes compared to the gold standard, FungisomeTM, indicating suitability of the nanoformulation for use in intramacrophage infections like VL. Additionally, in vivo biodistribution study revealed >95% RES targeting with high accumulation in infection reservoirs (liver and spleen) and significantly lower kidney and lung accumulation compared to liposomal FungisomeTM. This simple In situ approach allows preparation of AmB entrapped SLNs just prior to administration which enables point of care nanomedicine thereby also overcoming stability issues of nanoformulations, and aiding ease of translation from bench to bedside.
TARGETED SOLID LIPID NANOPARTICULATE DELIVERY SYSTEM OF Β- CARYOPHYLLENE OXIDE CONTAINING N-3 POLYUNSATURATED FATTY ACID AS ANTICANCER NANOCARRIER FOR TREATMENT OF BREAST CANCER
Bhagyashri Parab* , Dr Supriya Shidhaye
Vivekanand Education Society’s College of Pharmacy, Chembur, Mumbai- 400 074
Breast carcinoma is the heterogeneous tumour and considered as most prevalent female cancer worldwide. Current treatment regimen for breast cancer involves hormonal therapy, surgery, radiotherapy and chemotherapy. However there are several limitations of the conventional approaches for treatment such as resistance of Triple negative breast cancer towards hormonal therapy, cytotoxicity to normal cells, high cost. This necessitates need of an alternative treatment which offers lesser side effects, targeted action and lower cost. The present investigation aims at developing a formulation that addresses such major concerns in treating breast cancer. The formulation strategies involve: 1] Use of an herbal principle, β-caryophyllene oxide (BCPO): easy availability, low cost, proven anticancer activity. 2] Solid lipid nanoparticle (SLN) system for drug delivery: SLN will lead to protection of drug from degradation, provide stability to the drug after IV administration and prevent leaching of drug at non-targeted sites. 3] Use of n-3 Polyunsaturated fatty Acid (n-3PUFA), compound from natural origin: offers selective cytotoxicity towards cancer cells, acts as a lipid excipient with anticancer action. 4] Active Targeting of SLN with Folic acid: Targeting will aid in tumour site specificity resulting in reduced dose and side effects.
The developed SLN formulation will lead to significant improvement in available treatment options for breast cancer. The technology used is safe, scalable and has potential for clinical use. Also, it can act as platform technology for treatment of tumours at other sites.
DEVELOPMENT AND EVALUATION OF A NOVEL DELIVERY SYSTEM CONTAINING PHYTOPHOSPHOLIPID COMPLEX FOR SKIN LIGHTENING.
Supriya Shinde*, Saurabh Ahire, Mukesh Mohite, Revan Karodi.
Dr. D. Y. Patil, College of Pharmacy, Akurdi, Pune-411044.
Glycyrrhiza glabra and Solanum tuberosum are rich in anti-oxidant polyphenols helpful in prevention of skin darkening. Polyphenolic compounds have lower skin penetration and high polarity subsequently results in decreased cutaneous delivery. The present research is tried to develop a new phytophospholipid complex cream to enhance cutaneous delivery of polyphenolic compounds for sustained anti-oxidant action. Total phenolic content, total flavonoid content, and anti-oxidant assays (H2O2 scavenging activity) were done on different ratios of liquorice extract and potato juice. Evaluation parameters the complex was formulated as water-in-oil cream and evaluated for various parameters. Thus, developed polyherbal phytophospholipid complex cream safe and stable and it also exhibits a good potential as skin lightening cosmeceutical.
Raloxifene -Phospholipid Complex: Synthesis, Characterization and In Vivo Evaluation
Atul Jain1,2*, Teenu Sharma1,2, O P katare1,2 Bhupinder Singh1
1-University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies,
Panjab University, Chandigarh, India 160014
2-Chandigarh College of Pharmacy, Chandigarh Group of College, Landran, Mohali, India 160014
The current research work encompasses preparation of Raloxifene- phospholipid complex (RLX-C) for augmenting its biopharmaceutical performance in the management of breast cancer. Initially, in silico 3-D modelling was carried out employing Gaussian 09® program and in vitro “Job plot” was constructed in order to embark upon apt stoichiometry for preparation of RLX-C. Formation of the complex was ratified using diverse instrumental techniques and studies, like phase solubility, Gibbs-free energy and complexation rate. Pharmacokinetic studies in rats indicated significant improved biopharmaceutical performance, of the RLX-C. The evaluation using different in vitro quantitative cellular studies, including, cell uptake by Caco-2 cells, cellular cytotoxicity, apoptosis assay and reactive oxygen species assay using MCF-7 cells, also indicated markedly superior efficacy of RLX-C vis-a-vis pure RLX. All these inferences construe promising anticancer potential of developed RLX-C, thereby ratifying phospholipid complexation as efficient drug delivery strategy for improving the biopharmaceutical attributes of RLX.
FORMULATION OF ETRAVIRINE LOADED SELF MICRO EMULSIFYING DRUG DELIVERY SYSTEM IN A QBD FRAMEWORK AND IN VITRO AND INSILICO CHARACTERIZATION FOR ITS PERFORMANCE ATTRIBUTES
Kavitha A N*1, Janakiraman K2, Raman Dang3, Chandramouli R4
1-Department of Pharmaceutics, Krupanidhi College of Pharmacy, Bengaluru-560035, Karnataka, India,
2-Department of Pharmacy, Faculty of Engineering and Technology, Annamalai University, Tamil Nadu, India,
3-Principal, KLE College of Pharmacy, Bengaluru, Karnataka, India,
4-Department of Quality Assurance, Krupanidhi College of Pharmacy, Bengaluru-560035, Karnataka, India
* Kavitha A N
Associate Professor, Krupanidhi College of Pharmacy
Abstract:Adoption of Novel Drug Delivery System approaches to make therapeutically viable formulation of BCS class 2 & 4 is most followed approach. In this work the Etravirine (ETV) is formulated as a SMEDDS formulation in a lean QbD approach and it was characterized by conventional in vitro methods further augmented by Insilco approaches as well. The Critical Quality Attributes (CQAs) drawn from the Quality Target Product Profile (QTPP) were coded into the Extreme Vertices Mixture Design (EVMD) and the factors that would return with the required responses were identified and optimized. The optimized formulation was characterized by in vitro methods and also was further augmented with the application of Insilco prediction methods to understand the in vivo performance characteristics of the formulation.
HYDROXYAPATITE NANOPARTICLE-FUNCTIONALIZED THIOLATED POLYMER-BASED BIOCOMPATIBLE SCAFFOLD FOR SKIN TISSUE
Varsha S 1*, Devanand Kamnoore1
1Department of Pharmaceutics, M. S. Ramaiah University of Applied Sciences, Gnanagangothri Campus, New B.E.L. Road, M.S.R. Nagar, M.S.R.I.T Post, Bengaluru, Karnataka, India
In the present study, we have developed polymer hybrid scaffold functionalized with hydroxyapatite nanoparticles having an inherent effect of skin tissue regeneration and reepithelialization. Thiolated chitosan was combined with thiolated eudragit and polyethylene glycol to form the scaffold using the freeze-thawing method. During the freeze-thawing process, the scaffolds were functionalized with hydroxyapatite nanoparticles. The scaffolds were assessed for skin tissue regeneration activity on a rat model of excision wound and the molecular mechanism was conducted by in silico evaluation. FTIR and XRD studies confirmed the polymeric interlinking in the scaffold during the freeze-thawing method. SEM and microCT analysis indicated the functionalization of the nanoparticle on the scaffold moiety and a spongy structure of the scaffold with controlled pore intensity. In silico study in corroboration with in vivo evaluation indicated that the component of the scaffold act via controlling the actions of epidermal growth factor (EGF) and glycogen synthase kinase (GSK) and may prove to be a suitable material for tissue engineering.
FORMULATION OF ETOPOSIDE NANOSUSPENSION LOADED ORAL CAPSULES FOR ENHANCED BIOAVAILABILITY
Authors: Kshitija Phatak1*, Supriya Shidhaye 2, Shivali Tank 3
Department of Pharmaceutics, Vivekanand Education Society’s college of pharmacy
Institution Address: Vivekanand Education Society’s college of Pharmacy,
Hashu Advani Memorial complex, Chembur, Mumbai-400074
Limitations of several chemotherapeutic agents are associated with their bioavailability issues. Selected drug Etoposide has poor bioavailability due to its gastric degradation, p-gp efflux and low water solubility. The current work focuses on formulation of a Nanosuspension containing etoposide by Anti-solvent precipitation method in order to overcome the bioavailability issue. Formulation optimization was done by OFAT method and the optimised nanosuspension was converted into solid form by adsorption and filled in enteric coated capsules for easy oral administration. The optimized formulation showed particle size of 256.2 nm and PDI of 0.218 resulting in 20-fold solubility enhancement and 10% increase in permeability in comparison with the plain drug. The formulation gave 6% drug release in pH 1.2 and release of 91% drug release in pH 6.8 and was found to be stable as per ICH guidelines.
SUPERSATURATED SELF-EMULSIFYING DELIVERY SYSTEMS OF SORAFENIB TOSYLATE FOR IMPROVING ITS BIOPHARMACEUTICAL PERFORMANCE
Teenu Sharma1,3*, Atul Jain2, Om Prakash Katare 1, Bhupinder Singh1,2
1-University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh, India 160 014
2-UGC-Centre of Excellence in Applications of Nanomaterials, Nanoparticles & Nanocomposites (Biomedical Sciences), Panjab University, Chandigarh, India 160014
3-Chandigarh College of Pharmacy, Landran, Sector 112, Greater Mohali,
The current studies investigate the application of quality by design-enabled Type III-self emulsifying delivery system (Type III-SEDDS) of sorafenib tosylate (SFN) in improving its biopharmaceutical attributes. Type III-SEDDS have been established as the promising tool to augment oral bioavailability of poorly water soluble drugs, like SFN. The enormous potential of such systems is quite evident from the fact that most of the emulsifying products available in the market belong Type III-SEDDS, such as cyclosporine (Neoral®), ritonavir (Norvir®) and tipranavir (Aptivus®) [1, 2]. Furthermore, supersaturable systems have evolved as a vital modification of such Type III systems for improving the biopharmaceutical performance of drugs with high doses. As none of the literature reports on delivery of SFN, has investigated the incorporation of a unit human dose, i.e., 200 mg, in a single formulation till date, subsequent supersaturation of Type III-SEDDS(s) was carried out for the purpose. Thus, current studies report the potential of supersaturated Type III-SEDDS for ameliorating biopharmaceutical performance of SFN following oral intake.
Development and evaluation of herbal hydrogel spray for wound healing
Ankita Kawtikwar*, Tanaji Nandgude, Nateque Syed
Department of Pharmaceutics, Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, Maharashtra, India, 411018
Treatment of wound is essential as wound can also be lethal at some point in time if not treated properly. Couroupita guianensis extract has been shown to have exceptional antibacterial efficacy. The current investigation was aimed to synthesize the hydro alcoholic extract of C. guainensis and incorporate it into topical herbal hydrogel spray and perform its evaluations, which was achieved successfully. The optimized spray formulation gave uniform film at the site with burst release of 39.67% within 30 minutes which increases to 82.27% till 6hrs, it also have better tensile strength. Thus, C. guianensis hydrogel spray could be used as potential herbal wound healing agent in the management of wounds.
APPROPRIATED VIABILITY AND GERMINATION OF PROBIOTIC CELLS UPON INCORPORATION INTO SELF-PRESERVING EMULGEL FOR TOPICAL USE
Garima Sharma*, Manuhaar Sharma, Rishav Sood, Jayanthi Neelamraju, Suvarna G. Lakshmi, Ratna Sudha Madempudi, Praveen Rishi, Indu Pal Kaur#
* University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh,, India, 160014,
# Mentor: Chairperson, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh,, India, 160014,
Dermal disorders, owing to skin dysbiosis can be served by direct application of probiotics. However, there are few topical whole probiotic products in market because of (i) loss of viability during manufacturing and storage, and (ii) inadequate germination and retention on skin. Presently we report a novel (IPA 201811010395) emulgel incorporating whole cell Bacillus coagulans (Unique IS-2) for possible topical use. Developed emulgel was characterized for morphology, water activity, self-preservation, safety, stability and wound healing capacity. We successfully incorporated 97±5% (1.7x108CFU/g) Bacillus coagulans in honeycomb network of gelatin. Maintenance of CFU at 30±2°C, 65±5% RH for 3 months confirmed viability of incorporated probiotic. Low water-activity (0.66-0.732aw) and challenge test (0.0-0.5% viability at 28th day) confirmed its self-preserving nature. Early initiation (6h) and complete (24h) spore germination was evident on shaved rabbit skin. No cytotoxicity, dermal irritation or translocation in the blood and organs established its safety. Faster wound closure and reduced oxidative stress (LPO, catalase, SOD, glutathione reductase) in comparison to Soframycin® (1%w/w Framycetin) was observed in excision wound in mice. A whole cell probiotic formulation that is self-preserving, maintains probiotic viability, guarantees germination and has wound healing properties was successfully formulated.
FORMULATION AND EVALUATION OF CHLORTHALIDONE BUCCAL FILM FOR MANAGEMENT OF HYPERTENSION
Adesh Yelave*1, Geeta Bhagwat1
Department of Pharmaceutics, Humera Khan College of Pharmacy, Mumbai, Maharashtra, India-400102
Chlorthalidone is thiazide-like diuretic drug which is used in treatment of hypertension. It is BCS class IV drug and has high first pass metabolism leading to low bioavailability. The present work was undertaken to formulate mucoadhesive buccal film of chlorthalidone with an objective to improve therapeutic efficacy, patient compliance and bioavailability. Film formulations were prepared by solvent casting method using combination of hydrophilic polymers (HPMC E5 & HPMC K4M) with suitable plastisizer. Additives such as solubilizing agent to increase solubility and permeation enhancers such as bile salts to increase permeability were used. The developed films were evaluated for physicochemical characteristics such as thickness, content uniformity, surface pH, and in vitro drug release etc. The optimized formulation containing combination of hydrophilic (HPMC K4M) and hydrophobic (E5) showed good tensile strength, mucoadhesive strength and optimum in vitro diffusion results. The Ex vivo Drug permeation through bovine oral mucosa at the end of 8 hours was found to be 87.2 ±0.93%.