Drug Delivery Letters - Volume 5, Issue 1, 2015

Traditional approach of formulating a new drug product is an exhaustive task and involves a number of resources like man, money, time and experimental efforts. While, using this Quality by Design (QbD) approach one can get the pharmaceutical product of desired (best) quality with minimizing above resources as well as knowing the influence of one factor over the desired associated process. Hence aim of this study is the understanding of QbD approach to design product and manufacturing process to get desired pharmaceutical product. QbD follows the concepts of ICH guidelines (Q8, Q9 & Q10) which are essential for processing a pharmaceutical process. This review emphasizes on various aspects of keynotes of QbD like ascertaining drug product quality profile, priorizing input variables for optimization, modelization & validation of QbD methodology and in the last QbD validation, scale up and production as well as the software used for QbD. Hence, QbD approach is not only useful in facilitating comprehension of the products or process but also results in an excellent and economical product which follows federal compliance.

Pectin and its modified forms have been used in the formulation of controlled and sustained drug delivery systems in recent years. Due to its biodegradability, easy availability and other benefits it is one of the first choices for both consumers and research scientists. Ease in modifications of the acidic group into amide, ester or other forms leads to the alterations in physical and chemical properties of pectin which further increases its significance. Formulations based on pectin and its modified forms have shown a tremendous promise as novel biomaterials for targeting of the drugs and other emerging biomedical applications. Also pectin based products are utilized in cosmetic, textile and food industries. In this review we have summarized the sources of pectin, various extraction procedures, patents and different approaches to modify physio-chemical properties of pectin affecting the drug release. This paper emphasizes the practical utility of pectin and its modified form in pharmaceutical dosage forms.

The present study proposes to enhance solubility and eventually bioavailability of Atorvastatin Calcium (ATV) by preparing hot melt extrusion based orodispersible tablet (ODT). Tablet dosage forms displaying faster disintegration providing significant advantages over traditional techniques of solid dispersion (SD) were made by a speedy method. Dissolution analysis of the extrusion processed ATV using Soluplus in combination with Kolliphor TPGS (1:2:0.5) showed significantly increased dissolution rates and extent of supersaturation over pure drug. DSC and XRD studies revealed that ATV is converted to amorphous form during extrusion. A design of experiments (DOE) was conducted on ODT formulation to evaluate the effect of compression force and Kollidon CL-SF (super disintegrant) concentration on disintegration time, friability and hardness (p value <0.0001). The optimum formulation showed disintegration time 33±1.52 Sec, friability 0.91±0.035%, hardness 3.8±0.15 kg/cm2 and 91.18±1.2 % drug release within 15 min, thus comply US-FDA standard. The in vivo study revealed that the rate and extent of absorption of prepared tablet were higher than pure drug and marketed tablet. Cmax value of optimized formulation was 67.42±1.45 μg/ml, obviously higher than that of pure drug and marketed formulation which was 19.04±1.26 µg/ml and 56.11±1.64 µg/ml respectively. Similarly, Tmax value of former, 120 min significantly earlier compared with that of drug and marketed formulation which was 360 min and 240 min. Furthermore, Short-term accelerated stability study showed that tablets were stable at 40 °C and 75% RH as per ICH guideline.

The objective behind this study is to prepare a transdermal therapeutic system for aceclofenac and ameliorate to evaluate the influence of chemical permeation enhancer (oleic acid) on drug permeation through the human cadaver skin. The influence of permeation enhancer on permeation flux (J), enhancement ratio of flux (ERflux) and permeability coefficient (Pss) was compared with the control batch (without permeation enhancer) by using one-way ANOVA followed by multiple comparison analysis. The drug permeation from the formulations was best characterized by Higuchi diffusion followed by case II to super case II transport mechanism. The optimized patch containing 5% w/w concentration of permeation enhancer was able to increase more than fivefold of drug permeation. Skin irritation studies suggest that optimized transdermal patch is non-irritating and safe for dermal application. Scanning electron microscopy, differential scanning calorimetry and X-ray diffraction studies confirmed the amorphous state of aceclofenac in the transdermal patch. So it is concluded from the above research that the prepared transdermal therapeutic system was dermatologically safe and able to deliver effective amount of aceclofenac through the transdermal route.

The aim of the present research work was to develop and evaluate provesicular topical drug delivery system of indomethacin. The encapsulation of drug in vesicular structure prolongs the existence of the drug in the systemic circulation with improved bioavailability. The potential of proniosomes as a topical drug delivery system was explored by formulating proniosomal gel of indomethacin using coacervation-phase separation method with different ratios of sorbitan fatty acid esters (Span 60) and cholesterol. The formulations were characterized for various parameters like vesicle size and shape, drug entrapment, in vitro drug release profiles and vesicular stability at different storage conditions. In-vitro studies showed slow and sustained release of entrapped indomethacin. Stability studies for optimized proniosomal gel were conducted for 3 months. The current research work demonstrated that proniosomes are stable and promising topical drug delivery system for indomethacin.

The purpose was to develop monolithic gastroretentive system of rifaximin for prolonged release. Rifaximin (RFX) is a semi-synthetic antibiotic used in traveller's diarrhea and its local effect in stomach is desirable. A target quality product was defined and mucoadhesive strength, floating lag time and % drug release at three different time points were identified as critical quality attributes. Hydroxypropyl methylcellulose K100M (HPMC), sodium carboxymethylcellulose (SCMC) and sodium bicarbonate were identified as critical factors affecting the selected attributes based on initial screening. Drug-excipient compatibility was established using Fourier transform infrared spectroscopy (FT-IR). A three factor, three levels Box-Behnken design was used to obtain the design space and the desirable zone where all the set criteria for the formulation are met. Tablets of all the design point batches were studied for physical properties, floating lag time, total floating duration, ex vivo mucoadhesion and in vitro drug release. The robustness of the formulation in the desirable zone was established by preparing check point batch. The composition that had highest desirability was identified and studied further. The water uptake and erosion behaviour of the tablet was determined and correlated with percentage drug release. Antimicrobial study was performed to gauge the inhibitory effect of the developed formulation. The release mechanism was found to be of anomalous or non-fickian type. Stability study was performed at the conditions recommended by ICH guidelines and it was found that the values of critical responses did not change during the duration of stability study. RFX gastroretentive delivery system for twice a day dosing could be developed.

Multilayer tablet of tramadol hydrochloride was developed for the treatment of osteoarthritis. Multilayer tablet was comprised of immediate release layer, followed by drug-free retardant layers on either side of middle matrix layer. The sustained release effect was achieved by exploring the polysaccharide of tamarind kernel seed of Tamarindus indica. An extracted polysaccharide showed high swelling index and viscosity. Three-layer tablet system was optimized based on central composite design of two factors each at three levels, considering the amount of drug-free retardant layers, on either side (100 mg) of middle matrix drug polysaccharide layer (210 mg). Multilayer tablet was evaluated for hardness, thickness and drug content. Drug release is characterized by an initial rapid release (54% in acidic media), followed by a slow and again a second phase of relatively rapid release for 10 h. Presence of rat cecal content (2% and 4% w/v) in dissolution medium released the drug at a faster rate. Thus, inexpensive and abundantly available tamarind seed polysaccharide can be a good choice of polymer for dual release of multilayer tablet for arthritis patients.