Development and evaluation of a novel floating-osmotic capsule for zero order delivery of zidovudine
Vivek Chavda1*, Dr. Moinuddin Soniwala2, Dr. Divyang Dave3, Dr. Pragna Shelat4, Dr. Yamini D. Shah5, Dr. Praful Bharadiya6 and Dr. Mahesh T. Chhabria7
1-Assistant Professor, Department of Pharmaceutics, L M College of Pharmacy, Ahmedabad, India
2-Head, Department of Pharmaceutics, B K Modi Government Pharmacy College, Rajkot, India
3-Head, Department of Pharmaceutics, K B Institute of Pharmaceutical Education and Research, Gandhinagar, India
4-Ex Professor, Department of Pharmaceutics, K B Institute of Pharmaceutical Education and Research, Gandhinagar, India
5-Head, Department of Pharmaceutics, L M College of Pharmacy, Ahmedabad, India
6-Professor, Department of Pharmaceutics, L M College of Pharmacy, Ahmedabad, India
7-Principal, L M College of Pharmacy, Ahmedabad, India
Oral controlled release drug delivery have recently been of increasing interest in pharmaceutical field to achieve improved therapeutic advantages, such as ease of dosing administration, patient compliance and flexibility in formulation. Zidovudine is antiretroviral agent [NRTI] having problem of high hepatic first pass metabolism. It is having 35% Protein binding, so no depot action will be observed. For the antiviral therapy in the Hepatitis-B or AIDS maintenance of constant steady levels of the drug is highly desirable. To accomplish this objective it is decided to prepare Floating osmotic capsule which will be capable of releasing the drug with zero order release kinetics. Preparation of a novel capsule involves four steps where the pores in the cap have been prepared using standard gauze of different size. Cetyl alcohol was utilized as floating agent while a mixtures of sodium chloride and lactose were used as osmogent. Mannitol was used as diluent. For the optimization purpose Box-behenken design was used with three factors like Pore size, amount and ratio of Release at 1 h and 5 h were selected as dependent variables. The prepared dosage units were checked for its buoyancy parameters as well as release kinetics. Drug compatibility with excipients was checked by FTIR studies. The stability study conducted 3 month as per the ICH guidelines osmogent. The results suggest that, the drug was released by zero order kinetics. There is no floating lag time and floating tine was found to be more than 14 hr. in all the prepared batches. Alone sodium Chloride gave non zero order release hence a combination of sodium chloride and lactose were selected which gave zero order characteristic to the dosage unit. The formulations are also treated to Peppa’s plots by taking log percent drug release versus log time. The plots are found to be fairly linear and the regression values (R2 value) of all formulations were ≥ 0.97. The mean diffusional exponent values (n) ranged from 0.89-1.2 indicating that all these formulations presented a dissolution behavior controlled by zero order release. The stability study conducted as per the ICH guidelines and the formulations were found to be stable. From this study, it can be concluded that, the formulation retained for longer periods of time in the stomach and provides controlled zero order release of the drug. Hence improve the therapeutic effect of the drug by increasing its bioavailability.
DEVELOPMENT AND EVALUATION OF TOPICAL GEL INCORPORATING BASIL OIL MICROSPONGE CARRIERS WITH ENHANCED ANTIMICROBIAL ACTIVITY
Ritu Rathi*, Manju Nagpal, Sandeep Arora
Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India- 140401
Basil oil (BO), derived from Ocimum basilicum possess insect repellent and antimicrobial activities. However its high volatility, low aqueous solubility, low stability in light, oxygen and temperature restricts its application. The present study was aimed for the fabrication of BO loaded Ethyl cellulose (EC), and Polyvinylalcohol (PVA) microsponges (MS) with different ratios of EC: PVA for topical delivery. The Basil oil loaded microsponges (BOMSs) were prepared using quasi emulsion solvent evaporation technique employing EC as polymer, PVA as stabilizer and dichloro methane (DCM) as solvent. The effect of formulation variables such as amount of EC and PVA on the production yield, entrapment efficiency, particle size and drug release of MS was also investigated. The optimized MS were dispersed into Carbopol 934 gel and evaluated for drug release, skin irritation, antibacterial activity and photostability. Results revealed that the size of all prepared formulation lies in the micro range (12.39 to 64.03 µm), with good encapsulation efficiency (51.62 to 78.57 %) and controlled release profile (cumulative drug release upto 78.31 %). Field emission scanning electron microscopy depicted that MS were spherical in shape with a spongy structure. The optimized MS gel formulation was evaluated for antimicrobial assay. Furthermore, the results of photostability and stability analysis indicated enhanced stability of BOMS. Hence encapsulation of BO in microsponges resulted in efficacious carrier system in terms of stability as well as safety of this essential oil along with handling benefits.
SUBCONJUNCTIVAL CARBOPLATIN AND ETOPOSIDE POLYMERIC MICROPARTICLES FOR THE EFFECTIVE THERAPY AGAINST RETINOBLASTOMA
Deepa Warrier*, Rutika Godse, Abhijit De, Maitreyi Rathod, Ujwala Shinde
Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai, Maharashtra, India – 400098.
The purpose of this study was to develop carboplatin (CPT) and etoposide (ETP) loaded biodegradable polymeric microparticles as a combination therapy for retinoblastoma via subconjunctival route and to evaluate it by in vitro and in vivo methods. CPT and ETP loaded PLGA microparticles (CE-MIP) were prepared by emulsification-spray drying technique by optimizing various process and formulation parameters. The optimized drug loaded PLGA microparticles were characterized for particle size, zeta potential, entrapment efficiency and in vitro release. In vitro cytotoxicity studies of CE-MIP and plain drugs were carried out in Y-79 and WERI-Rb cell lines. Anti-tumor efficacy of CE-MIP was also investigated by carrying out Soft agar assay study on Y-79 cell line. The pharmacokinetic parameters of vitreous and plasma drug levels on subconjunctival administration of CE-MIP and free drug were assessed in Sprague Dawley rats. The in vivo efficacy of CE-MIP in the treatment of orthotropic retinoblastoma in nude mice via subconjunctival route was evaluated. The particle size of CE-MIP was found to be 3-14 µm and the zeta potential values ranged between -23.0 to -34.2 mV indicating stability. DSC and XRD studies indicated that CPT and ETP were present in the amorphous phase and may have been homogeneously dispersed in the PLGA matrix. SEM micrographs showed discrete and homogenous particles. The entrapment of ETP and CPT in PLGA microparticles was found to be more than 80% and more than 60% respectively. Drug release study showed that CE-MIP released CPT in 4 h and sustained the release of ETP up to 72 h. In vitrocytotoxicity studies CE-MIP showed greater anti-cancer effect (25.33% cell viability) compared to plain drug mixture (38.56% cell viability) in Y-79 cells (200 μM concentration). In WERI-Rb cell lines, the CE-MIP and plain drug mixture at 100 μM showed % cells viability as 37.82% and 66.08% respectively. In the soft agar assay, the CE-MIP treatment demonstrated a significant reduction in the number of colonies (~50% reduction) formed as compared to control. Also, the apoptotic effect of CE-MIP (15.7%) was greater compared to that of control (7.9%). The pharmacokinetic study showed that CPT concentration in the vitreous humor was far higher than that in the plasma, indicating the possibility of minimizing systemic side effects. Mean tumor burden in the CE-MIP treated eyes was significantly smaller compared to the untreated control eyes showing the anti-tumor efficacy of developed CE-MIP. Taken together, the study demonstrated that CPT-ETP/PLGA MIP based subconjunctival drug delivery system holds significant potential towards the treatment of retinoblastoma.
DEVELOPMENT AND INVESTIGATION OF NOVEL DRUG ABUSE DETERRENT TECHNOLOGY
Jayendrakumar D. Patel*$, Rakesh P. Patel$
$: Institute Address: Ganpat University, Faculty of Pharmacy, Ganpat Vidyanagar, Mehsana – Gozaria Highway, Kherva, Gujarat, India – 384012
Today the prescription opioids are the only primary treatment and Boon for the more than 1.5 billion patients suffering from chronic pain, which have not significantly changed in the past decade. However, along with continuing growth of opioid market, opioid abuse has led to growing health and socio-economic problem world-wide. In India, ~5.63% of Indian Population with age range 10-75 Years are affected with Drug Abuse. Severity of drug abuse crisis in the world can-be estimated from that in 2017, US declared Opioid Crisis as “National Health-Emergency” which costing the U.S. more than $100 billions/year. Therefore, this is a real time and chance for Pharmaceutical Industry to save our society from the combat of the opioid epidemic but currently, none of pharmaceutical formulation available in market that effectively mitigate both, overdose abuse-crisis and deterring abuse after tampering with the dosage form.
Controlled bimatoprost release from graphene oxide laden contact lenses: In vitro and in vivo studies
Ditixa Desai a *, Parth Soni a, Dinesh Shah b, Mark Willcox c, Furqan Maulvi a
a Maliba Pharmacy College, Uka Tarsadia University, Surat 394350, India
bDepartment of Chemical Engineering and Department of Anesthesiology, University of Florida, Gainesville, FL, USA 32611
cSchool of Optometry and Vision, University of New South Wales, Sydney, New South Wales 2052, Australia
* Corresponding author at: Maliba Pharmacy College, Uka Tarsadia University, Surat 394350, India
Ocular drug delivery using contact lenses may be able to substitute for eye drop therapy. However, issues with hydrophobic drugs such as low drug uptake using a simple soaking method into preformed contact lenses and alteration in the swelling and transmittance of lenses restricts the application for drug delivery. This research uses graphene oxide (GO) to control the release of bimatoprost from contact lenses along with improvements in the drug uptake, and lens swelling and transmittance. GO was loaded into silicone hydrogel contact lenses during polymerization. These lenses when soaked in bimatoprost solution, improved its in vitro release profile. Adding both bimatoprost and GO during polymerization (DL-GO-BMT) significantly decreased the loss of drug during extraction and sterilization in comparison to contact lenses (DL-BMT) without GO. As the amount of GO was increased, the DL-GO-BMT lenses showed a significant decrease in the burst and cumulative release of bimatoprost. GO improved contact lens swelling due to its water binding capacity and lens transmittance due to the molecular dispersion of bimatoprost on the surface of the GO which prevented the local precipitation of the drug. Ocular irritation and histopathology reports demonstrated the safety of GO contact lens. The in vivo pharmacokinetic studies in the rabbit tear fluid showed significant improvement in MRT and AUC with DL-GO-0.2µg-BMT-100 contact lens in comparison to eye drop solution. The study demonstrated that the addition of GO to contact lenses can control the release of bimatoprost as well as improved the lens swelling and transmittance.