Recent Patents on Drug Delivery & Formulation (v.10, #3)

Meet Our Editorial Board Member by Marcos L. Bruschi (175-176).

Liposomal Drug Delivery System for Cancer Therapy: Advancement and Patents by Sheetal Jha, Pramod K. Sharma, Rishabha Malviya (177-183).
Background: In this review article, authors reviewed about the liposomes which are amongst various drug delivering systems for the delivery of the therapeutic agents at the target site.

Methods: Advances in liposomal drug delivery systems for the cancer therapy have enhanced the therapeutic levels of the anticancer moieties. Liposomes show promising action on the tumor by incorporating less amount of drug at the target site, with minimum toxic effect and maximum therapeutic effect and thereby enhancing the bioavailability.

Results: Liposome-based drug delivery systems provide the potential to elevate the effect of drug concentration in tumor cells. Manuscript briefly describes the role of liposomes in cancer therapy and various patents based on the same.

Multi-particulate Systems: Cutting-edge Technology for Controlled Drug Delivery by Sarika Wairkar, Ram Gaud, Adhithi Raghavan (184-191).
Background: In the last two decades, multi-particulate dosage forms have caught the attention of formulation scientists due to their tremendous potential as a drug delivery system with a broad range of applications.

Methods: Recent patented technologies are focused on designing multi-particulate systems that can enhance therapeutic efficacy and oral bioavailability with minimum systemic toxicity. The technologies offer opportunities to the manufacturers for increasing their market share, especially for competitive generics, and also establishing intellectual property positions.

Results: The present paper provides an overview of advanced technologies and patents, based on different principles, for designing multi-particulate dosage forms. The review covers basic characteristics of the current technologies, the mechanisms by which they overcome the limitations of conventional oral dosage forms, and their applications.

Conclusion: Comprehensive knowledge of these technologies will expedite further development and platform technologies for multi-particulate controlled drug delivery systems.

Quality by Design (QbD) Approach for Development of Co-Processed Excipient Pellets (MOMLETS) By Extrusion-Spheronization Technique by Hetal Patel, Kishan Patel, Sanjay Tiwari, Sonia Pandey, Shailesh Shah, Mukesh Gohel (192-206).
Background: Microcrystalline cellulose (MCC) is an excellent excipient for the production of pellets by extrusion spheronization. However, it causes slow release rate of poorly water soluble drugs from pellets.

Co-processed excipient prepared by spray drying (US4744987; US5686107; WO2003051338) and coprecipitation technique (WO9517831) are patented.

Objective: The objective of present study was to develop co-processed MCC pellets (MOMLETS) by extrusion-spheronization technique using the principle of Quality by Design (QbD).

Methods: Co-processed excipient core pellets (MOMLETS) were developed by extrusion spheronization technique using Quality by Design (QbD) approach. BCS class II drug (telmisartan) was layered onto it in a fluidized bed processor.

Results: Quality Target Product Profile (QTPP) and Critical Quality Attributes (CQA) for pellets were identified. Risk assessment was reported using Ishikawa diagram. Plackett Burman design was used to check the effect of seven independent variables; superdisintegrant, extruder speed, ethanol: water, spheronizer speed, extruder screen, pore former and MCC: lactose; on percentage drug release at 30 min. Pareto chart and normal probability plot was constructed to identify the significant factors. Box-Behnken design (BBD) using three most significant factors (Extruder screen size, type of superdisintegrant and type of pore former) was used as an optimization design. The control space was identified in which desired quality of the pellets can be obtained.

Conclusion: Co-processed excipient core pellets (MOMLETS) were successfully developed by QbD approach. Versatility, Industrial scalability and simplicity are the main features of the proposed research.

Introduction: The solid lipid nanoparticles (SLNs) of Acyclovir (ACV) were fabricated with Soya lecithin and Fractionated Coconut oil (medium chain glyceride) as a first time combination.

Methods: The research was focused on developing ACV-SLN by using high pressure hot-homogenization technique. The ingredients were used in different concentrations and ratios to identify the best formulation design. The tween 80 and Pluronic F-68 were used in various concentrations in formulation design to assess the impact on the fabrication and evaluation of SLNs. The impact of nanotechnology gain to play a vital role in the topical pharmaceutical products and the related patents will play a significant role in related industries.

Results: The SLNs were subjected to various characterization techniques such as XRD, FTIR, Master sizer analysis and zeta potential. The mean particle size was determined by master sizer and zeta sizer. Transmission electron microscopy (TEM) was used as a tool to analyze the morphology and other features. The zeta potential and drug entrapment efficiency (EE%) were also determined for the prepared ACV-SLNs. The efficiency of drug release from prepared formulations was studied by using in vitro study with the utilization of dialysis membrane technique. SLN dispersions exhibited the average size in nano range.

Conclusion: SLNs with small particle size found to have predetermined encapsulation efficiency, and relatively high loading capacity and predetermined in vitro drug release profile.

Background: The purpose of this study was to investigate the application of a controlled porosity osmotic tablet (CPOT) utilizing solid dispersion (SD) of poorly soluble drug. The patents on Cyclobenzaprine HCl (US4968507 A) and Venlafaxine salts (EP 2085078 A1) helped in the selection of drug and polymers.

Method: The SDs having different ratio of drug to carrier (PVP K 30) were prepared by kneading method and optimized. Effect of three independent variables, total amount of osmogen (mannitol& potassium chloride), total amount of polymer (polyethylene oxide WSR 301, hydroxy propyl methyl cellulose K100 M) and polymer1: polymer 2 ratio were investigated using Box Behnken design. Core and coated tablets were evaluated for various parameters. In-vitro drug release profiles of CPOT tablets were compared with reference product Diffcore tablet, Lamictal XR (GlaxoSmith Kline Inc., USA).

Results: All formulations showed acceptable parameters. Drug release from CPOT was determined as complete, zero order and pH-independent within the physiological pH range of the GI tract. Drug release was directly proportional to initial level of polymers and osmogens.

Conclusion: The present results confirmed that prepared LTG SD serves as solubility modulator. Further, CPOT of LTG based on SD proved to be successful in delivering the drug in a controlled manner ensuring the once daily dosing for the treatment of convulsive disorders.

Development of Self Emulsifying Formulations of Poorly Soluble Naproxen for Enhanced Drug Delivery by Subhash C.B. Penjuri, Damineni Saritha, Nagaraju Ravouru, Srikanth R. Poreddy (235-244).
Background: The objective of this investigation was to develop a self emulsifying drug delivery system (SEDDS) of naproxen, a poorly water soluble drug, which could improve its solubility and oral bioavailability.

Methods: The recent patents on SEDDS of abiraterone acetate (WO2014/009434 A1) and tamoxifen (WO2013/0080083) helped in selecting the naproxen and excipients. Phase diagrams were constructed and the formulations were taken from the micro emulsion region. Formulations were subjected to thermodynamic stability, dispersibility and precipitation tests for optimization. Physico chemical characterization was carried out by FTIR and DSC studies. The selected SEDDS consisted of IPM+labrafac lipophile WL 1349, tween 80, PEG 400 and naproxen. The optimized formulation has globule size- 187.6 nm, zeta potential- -9.81 mv, viscosity- 1.772 cps and infinite dilution ability.

Results: In vitro drug release was 98.21% and was found to be significantly different from the marketed product and plain drug. After oral administration in rats the SEDDS of naproxen showed anti inflammatory activity (69.82%) which was much improved as compared to the marketed formulation. The Cmax, AUC0t of naproxen was boosted with SEDDS to 133.63 g/ml and 698.29 hr. g/ml respectively. The optimized formulation was found to be stable for 6 months during stability studies conducted according to the ICH Q1A (R2) guidelines.

Conclusion: Thus this developed self emulsifying drug delivery system may be a useful tool to enhance the solubility of oral poorly water soluble drug naproxen.

Self-emulsifying Pellets Prepared by Extrusion/Spheronization: In vitro/In vivo Evaluation by Mohammad A. Rahman, Mohammad Mujahid, Arshad Hussain (245-252).
Aims: The purpose of the current study was to investigate the feasibility of producing solid self-emulsifying pellets using the extrusion/spheronization technique with an aim to increase the bioavailability of selected drug and also to encounter the problems associated with liquid lipid formulations. Selfemulsifying formulations are experiencing a very active development as reflected by the numerous publications and patents being granted on these systems. The patents on self-emulsifying formulation (US20036630150) and (US20006054136) helped in selecting the drug and excipients.

Material and Methods: These pellets were prepared using liquid SNEDDS (24.59 % LBF M 2125 CS + Maisine35-1; 1:1 ratio) (oil), 50.27 % Labrasol (surfactant) and 25.13% Lauroglycol 90 (cosurfactant), adsorbent (silicon dioxide), pellet forming excipient (microcrystalline cellulose), binder (pregelatinized starch), disintegrant (croscarmelose sodium) and lubricant (corn starch).

Results: The resulting self-emulsified pellets loaded with about 32% liquid SNEDDS exhibited uniform pellet size and round shape, droplet size distribution following self-emulsification was nearly same to the liquid SNEDDS (26.5 nm and 24.8 nm, respectively). The in vitro release was significantly higher than the plain drug (p<0.01). AUC0-36h of sertraline from the pellets showed about 5-fold greater than the plain drug and no significant difference compared with the liquid SNEDDS (p>0.05).

Conclusion: In conclusion, spherical pellets with low friability and self-emulsifying properties can be produced by the standard extrusion/spheronization technique. The pellets are capable of transferring lipophilic compounds into the aqueous phase and have a high potential to increase the oral absorption of lipophilic drugs.

Patent Selections: (253-254).