Drug Delivery Letters - Volume 5, Issue 2, 2015

Background: In the present competitive situation, pharmaceutical companies all over the world are mainly focusing on the quality of product for maximum consumer acceptance and market share. Regulatory authorities are also trying to develop the pharmaceutical manufacturing process and technology, which is more concerned about the quality. Methods: Various online data and industrial requirements were reviewed and based on the today’s industrial need the paper was summarized. One of the important steps in creation of quality products was implementation of Quality by design (QbD) in pharmaceutical manufacturing. Results: The whole concept of the QbD is mainly concerned with the thorough understanding of the product and process based on knowledge and risk management. Further the process validation and continual improvement in product and process are other important aspects of QbD. After the end of 2013, the USFDA had started stressing upon the manufacturers to strictly implement the QbD. Conclusion: This review paper discusses in brief about the important stages of QbD, QbD in active pharmaceutical ingredient (API) manufacturing and QbD in case of sterile dosage form manufacturing (extractables and leachables from container closure system; and sterility).

Background: The aim of the present study was to design and characterize the enteric coated mucoadhesive microcapsules of esomeprazole magnesium by solvent evaporation technique using drug, ethylcellulose and mucoadhesive polymer of 1:1:1 ratio for improving the mean gastric residence time and oral bioavailability of the drug. Methods: Characterization of the mucoadhesive microcapsules through FT-IR, and DSC studies showed lack of any significant interactions among drug and polymers, followed by complete encapsulation of the drug in the prepared formulation. Scanning electron microscopy indicated spherical morphology of the prepared formulation with intact nature of the outer coat. Results: This system remains in close contact with the absorption tissue and the mucous membrane, releasing the drug at the action site leading to enhancement in the oral bioavailability due to avoidance of hepatic first-pass metabolism. Physiological variables (i.e., mucin turnover from the mucus layer) plays major role in the estimation of mucoadhesive strength of formulation, by mucin turnover ensures significant amount of soluble mucin available for interaction with mucoadhesive polymer. Conclusion: The selected optimum formulation (F3c) identified from the current studies protected rat stomach ulcer induced by ethanol vis-à-vis the aqueous solution of the drug owing to optimum mucoadhesion, swelling and sustain drug release characteristics by prolonging the duration of action of the drug. Stability studies as per the ICH guidelines showed no significant alteration in drug content and release characteristics indicating stable nature of the optimized microcapsule formulation.

Background: Emergence of new synthetic methods has given great impetus and momentum to nanotechnology which has revolutionized almost all disciplines of science and technology including medicine and pharmacy. The most fascinating aspect of nanomaterials is their vital role in drug delivery technology that makes use of them as drug carrying vehicles and delivers the carried drug to the diseased site in pre-determined amount. The present work aims at designing genipin crosslinked nanocarriers of gelatin and studying release of cisplatin drug under varying experimental conditions. Methods: The genipin crosslinked nanoparticles of gelatin were prepared by emulsion crosslinking method and the nanoparticles were characterized by techniques like FTIR, SEM, TEM and particle size analysis. The nanocarriers were loaded with cisplatin and the release of drug was monitored spetrophotometrically. Results: The size of nanoparticles was found up to 150 nm and the FTIR spectra confirmed the crosslinking of gelatin by genipin. The release of cisplatin was found to increase with increasing percent loading of drug. The amount of released cisplatin was significantly dependent on the amount of gelatin and genipin. The amounts of released drug at acidic and alkaline pH were greater than that released at neutral medium. The drug was found to decrease with increasing temperature of the release medium. Conslusions: The emulsion crosslinking of gelatin with genipin results in a swelling controlled drug delivery system which may be successfully used to achieve controlled release of cisplatin type of drug. The nanoparticles produced are quite nanosize in dimension and offer greater loading of drug which may desirably be released with precise control over its amount.

Glibenclamide is a second generation hypoglycaemic agent used for the management of Diabetes Mellitus. In the present study, matrix type transdermal patches of Glibenclamide were prepared by solvent casting technique using various combinations of hydrophobic (ethyl cellulose) and hydrophilic (Polyvinyl pyrrolidone) polymer, named as batch A (without penetration enhancer) and batch B (with penetration enhancer). Initial studies included with the compatibility among the drug and the polymers. All fabricated patches were subjected to physicochemical characterization, in vitro performance of transdermal patches and stability studies. An optimized ethyl cellulose and polyvinyl pyrrolidone composition was chosen to measure the effect of vegetable oils as penetration enhancers on the drug permeation across Wistar rat skin and on the skin itself. In vivo acute hypoglycemic activity in Wistar rats using streptozotocin-induced diabetes model was also performed.The results indicated no interaction between the drug and the polymers. The data obtained from the physicochemical characterization suggested less variations among the patches. Percentage cumulative drug release from the in vitro study depicted the effect of polyvinyl pyrrolidone, on increasing its concentration with respect to ethyl cellulose increases the release of Glibenclamide from the matrix. Significant effect of vegetable oils on the lipid and protein framework of the skin was seen which results in approximately 1.3 fold times increase of Glibenclamide flux. The hypoglycemic activity revealed the significant reduction in blood glucose levels (≈55% at 12th hour) from the transdermal patches which proves the sustained release of Glibenclamide over a prolonged period of time. Thus combination of polymers with the use of vegetable oils as penetration enhancers could be used to prepare stable and effective Glibenclamide transdermal patches which exhibit better control of the blood glucose level in diabetes mellitus.

This study investigated the in vitro antimicrobial and antiproliferative activities of the methanol extract and of purified compounds from fruits of Ficus bubu Warb. Extensive chromatographic isolations provided two stilbenes, that were identified by NMR and mass spectrometry as trans-resveratrol 4a and piceid 7a, in addition to several other chemical compounds. It was found that trans-resveratrol 4a exhibited the best antimicrobial activity (MIC value of 11 μg/mL), and presented a good anticancer activity (IC50 of 36 and 57 µM against A549 and SK-MEL-28 cancer cell lines, respectively). The peracetylation of isolated compounds was found to increase their antiproliferative activity. The peracetylated piceid 7b was the most efficient with an IC50 of 16 µM against the cells of melanoma skin cancer SK-MEL-28 while the starting crude extract did not show any activity. In contrast, this crude extract exhibited good antimicrobial activity against all tested strains. The present study constitutes the first phytochemical report on the methanol extract from F. bubu fruits and establishes the preliminary basis for its medical use. Finally, it is worth mentioning that polyphenolic piceid 7a is isolated for the first time from a plant of the genus Ficus.

Background: Temperature-sensitive liposomes (TSLs) containing chemotherapeutic drugs offer the prospect of increased drug delivery and bioavailability at the diseased sites. This concept is applied to hydrophilic drugs, which can be encapsulated in the inner water-rich lumen of the liposomes. In order to extend the concept of TSL to a hydrophobic drug, such as docetaxel (DTX), this drug was modified at the hydroxyl group in the C-2’ position into an N-methyl-piperazinyl butanoic acid ester. This modification resulted in a more hydrophilic DTX derivative (MPB-DTX) and hence, enabled stable encapsulation of MPB-DTX in the interior of liposomes. Under hyperthermic conditions, MPB-DTX will be released from the interior of TSL and activated in situ by pH 7.4 and esterases in vivo. Herein, the development and characterization of TSLs containing MPB-DTX [TSL(MPB-DTX)] for hyperthermiamediated drug delivery were described. Methods: TSL(MPB-DTX) was formulated with DPPC, MSPC, DSPE-PEG2000 and DPPE-rhodamine at a molar ratio of 85:10:5:0.2. The hydrodynamic radii (rh) and melting phase transition temperature (Tm) of TSLs were characterized using dynamic light scattering (DLS) and differential scanning calorimetry (DSC), respectively. The in vitro release kinetics as well as the blood kinetics and biodistribution of TSL(MPB-DTX) were investigated in rats. Results: The rh and Tm of TSLs were 62±3 nm and 41±0.1 °C, respectively. At 37 °C, TSL(MPB-DTX) exhibited a maximum of 38±5% MPB-DTX release in HBS supplemented with 50% FBS at pH 7.4 within one hour. At 42°C, rapid drug release to 66% could be achieved within minutes while 34% of the MPB-DTX remained with the liposomes. In nude rats, TSL(MPB-DTX) was shown to have a circulation half-life of 40±8 min while free MPB-DTX was cleared from the circulation within the first 10 min after injection. Biodistribution results confirmed clearance of the MPB-DTX from the circulation and low accumulation of MPB-DTX at non-clearing organs for both the TSL and free formulation. Conclusions: The rapid but incomplete release of TSL(MPB-DTX) indicates potential for a two-step delivery approach: (i) hyperthermia-mediated intravascular MPB-DTX release and (ii) enhanced accumulation of TSL(MPB-DTX) in tumor tissue via enhanced permeability and retention mediated uptake.

Background: 7–hydroxy–14H–naphtho[2,3–a]phenothiazine–8,13–dione (AQATP) was synthesized by using iodobenzenediacetate as catalyst from 1,4–dihydroxyanthraquinone (1,4–AQ) which was isolated from Cassia tora seeds. Methods: They were then characterized by various spectral techniques. Single crystal X-ray diffraction studies revealed that AQATP crystallizes in orthorhombic space group. ADME Test was performed to determine pharmacokinetic parameter using MedChem designer software. The In silico docking studies were performed to find out the anticancer effect of 1,4–AQ and AQATP using iGEMDOCK software taking CK2 protein as the target. In silico anti-inflammatory study was also carried out by means of the same software taking COX–2 and LOX–5 enzymes as the targets. Results: It was found that the derivative exhibited more binding affinity than the parent compound for both anticancer and anti-inflammatory activities. In vitro anticancer activity in colon cancer cell lines, anti-inflammatory activity by denaturation, COX and LOX assay were performed on AQATP. Conclusion: Results from both computational and in vitro analysis suggest that structural modification of 1,4–AQ could be considered as a good strategy to obtain a lead molecule for drug discovery.