Topical Semisolid Formulations Research Articles

COMPARATIVE STUDY OF SEMI-SOLID BASES OF NAPROXEN: PHARMACEUTICAL TECHNOLOGY ASPECTS

Objective: The main objectives of the present investigation work included that the preparation of a suitable naproxen semi-solid dosage form by using different types of semi-solid bases (gel bases, ointment bases) for topical application for the effective treatment of muscle aches. Methods: Different types of semi-solid bases (gel bases and ointment bases) were successfully prepared by the incorporation method to know the effect of semi-solid bases on drug release from topical semi-solid formulations. In all formulations, the drug was added by the levigation method. An evaluation study of prepared formulations, includes physical appearance, spreadability, extrudability, pH was conducted according to official methods. Results: Percent drug release of all formulations was conducted by taking diffusion cells with cellophane membrane and results showed that gel-based formulations showed more drug release than ointment-based formulations. Carbopol gel base (F1) showed more drug release (98.76 %), simple ointment base formulation (F8) showed least drug release (25.11%). From the stability studies reports at various temperature and humidity conditions it is evident that all formulations are stable for one month. In all the formulations, the drug content was observed at 95.75%. Conclusion: Finally concluded that the NXN topical dosage forms can be prepared by using gel-type bases preferably than ointment bases to release more drug from formulations.

Application of Confocal Raman Microscopy for the Characterization of Topical Semisolid Formulations and their Penetration into Human Skin Ex Vivo

PurposeThe quality testing and approval procedure for most pharmaceutical products is a streamlined process with standardized procedures for the determination of critical quality attributes. However, the evaluation of semisolid dosage forms for topical drug delivery remains a challenging task. The work presented here highlights confocal Raman microscopy (CRM) as a valuable tool for the characterization of such products.MethodsCRM, a laser-based method, combining chemically-selective analysis and high resolution imaging, is used for the evaluation of different commercially available topical acyclovir creams.ResultsWe show that CRM enables the spatially resolved analysis of microstructural features of semisolid products and provides insights into drug distribution and polymorphic state as well as the composition and arrangement of excipients. Further, we explore how CRM can be used to monitor phase separation and to study skin penetration and the interaction with fresh and cryopreserved excised human skin tissue.ConclusionThis study presents a comprehensive overview and illustration of how CRM can facilitate several types of key analyses of semisolid topical formulations and of their interaction with their biological target site, illustrating that CRM is a useful tool for research, development as well as for quality testing in the pharmaceutical industry.Graphical abstract

Silver oxynitrate gel formulation for enhanced stability and antibiofilm efficacy.

Topical semi-solid formulations are ubiquitous in personal care and pharmaceutical applications. For centuries, these topical formulations have facilitated delivery of active ingredients such as botanical oils, medicinal extracts and more recently antibiotics and biologics. Numerous strategies exist for the stabilization and release of these active ingredients from semi-solid formulations, namely, inclusion of anti-oxidants and surfactants to extend shelf life and facilitate delivery respectively. However, in the instance where the active ingredient itself is an oxidizing agent, traditional strategies for formulation have limited utility. Recent evidence has highlighted the exceptional efficacy and safety of highly oxidizing silver compounds, containing Ag2+ and Ag3+. These higher oxidation states of silver provide antimicrobial and antibiofilm activity without impairing healing. However, as strong oxidizing agents, their application in medical device and pharmaceutical formulations such as semi-solid formulations are limited. The present study reports on the development of a silicone-based gel formulation of silver oxynitrate (Ag7NO11), a higher oxidation state silver complex. In this study the chemical stability of silver oxynitrate was examined through solid state characterization with X-ray diffraction, formulation stability and microstructure of the semi-solid gel evaluated through various rheological techniques, therapeutic functionality of the semi-solid formulation investigated through in-vitro planktonic and biofilm antimicrobial studies, and biocompatibility assessed though in-vitro mammalian fibroblast and in-vivo porcine wound healing models. Enhanced stability of silver oxynitrate within the semi-solid formulation was observed over a four-month X-ray diffraction study. At the end of the study, silver oxynitrate was identified as the principal diffraction pattern in the semi-solid formulation where argentic oxide diffraction peaks were observed to be dominant in silver oxynitrate powders alone. Viscoelastic or gel-like behavior of the formulation was observed under dynamic rheological study where the storage modulus (G' = 1.77±0.02×104 Pa) significantly exceeded the loss modulus (G″ = 4.89±3.72×102 Pa) (p<0.0001). No significant (p=0.84) change was observed in the apparent viscous response within the last three months of the study period indicative that the formulation approached a steady rheological state. The silver oxynitrate semi-solid formulation provided sustained in-vitro antimicrobial activity (>99.99% kill) over seven days with a significant reduction in biofilm within 6h (p<0.001). In-vitro mammalian fibroblast studies demonstrated the formulation to be non-cytotoxic and 100% epithelialization was observed within a six-day in-vivo porcine deep partial-thickness wound. The improved chemical stability, biocompatibility and efficacy results indicate that silicone gel semi-solid formulation may be a promising medicinal configuration to facilitate expansion of the clinical use of silver oxynitrate.

Innovative drug vehicle for local treatment of inflammatory skin diseases: Ex vivo and in vivo screening of five topical formulations containing poly(lactic acid) (PLA) nanoparticles

One of the main goals in the galenic development of innovative topical treatment options for inflammatory skin diseases such as psoriasis and atopic dermatitis is to selectively deliver the drug at the inflammation site. Recent studies have highlighted the beneficial use of polymeric nanoparticles for anti-inflammatory therapy and topical anti-inflammatory drug delivery due to their ability to form a drug reservoir retaining the drug locally at the site of action. Our approach consisted in designing innovative topical semi-solid formulations of poly(lactic acid) (PLA) nanoparticles as anti-inflammatory drug vehicles for local treatment of inflammatory skin diseases. In the course of this work, five topical formulations containing fluorescent PLA nanoparticles were initially developed, and then screened depending on their physico-chemical properties, toxicity and delivery efficacy. The penetration and permeation of a fluorophore vectorized by PLA nanoparticles into healthy and inflammatory skin were assessed using an alternative device to classical Franz cells: VitroPharma. All these investigations led to the selection of two satisfactory formulations out of five initial candidates.

Topical Semisolid Formulations of Hirsutenone and Accelerated Stability Assessment

To develop a topical preparation of hirsutenone (HST), a natural immunomodulator, we formulated oleaginous ointments and creams and assessed their stability in terms of shelf‐life. Ointments were prepared by mixing the molten lipid phase of white petrolatum and white beeswax with glycerin and propylene glycol, in which HST was dissolved with ascorbyl palmitate (AP), butylated hydroxyl toluene (BHT), or ethylenediaminetetraacetic acid (EDTA) as an antioxidant. Reference oil‐in‐water creams were formulated by conventional emulsification. The ointment and cream formulations were subjected to accelerated stability testing at 40 °C. At appropriate time points, test samples were dissolved in organic solvent, diluted with methanol, and filtered prior to high‐performance liquid chromatography (HPLC). The degradation of HST in cream and ointment formulations followed first‐order kinetics. The rate constants (day−1) of HST in cream and ointments were 1.71 × 10−2 and 0.67 × 10−2, respectively, revealing a 2.5‐fold greater half‐life in ointments than in creams. Although AP and BHT had no effect on chemical stabilization of ointments, EDTA enhanced the stability of HST at 40 °C. The shelf‐lives of HST formulations were estimated by the Q10 method. Assuming a Q10 value of 2, the shelf‐lives (days) of cream, ointment, and ointment with EDTA at 25 °C were 14.99, 38.23, and 44.19, respectively. At 4 °C, the shelf‐life of HST in ointment with EDTA was extended to 220 days. Even though the stability of HST was somewhat increased by the ointment formulation and further improved by adding EDTA, alternative approaches are needed to increase stabilization.

The Evaluation of Concentration - In-Vitro Release Relationship for Topical Semisolid Formulations of Sodium Cromoglycate.

Purpose. The aim of the study was to evaluate the concentration - in-vitro release relationship for topical semisolid formulations of sodium cromoglycate. Materials / Methods. According to usual pharmaceutical compounding practice, commercially available cosmetic emulsions were used as vehicles for topical semisolid dosage forms containing 0.5, 2, 4 and 10% disodium cromoglycate (CS). The in-vitro release profiles and structural parameters of the resulting formulations was evaluated in a correlated manner, in order to reveal potential differences in the in-vivo performance. Results. Depending on the hydro-lipophilic characteristics of the vehicle and on the quantity of drug dissolved or dispersed, the structure and the release kinetics are distinct. Conclusions. The results suggested that current lack of an unitary approach for the compounding of semisolid dosage forms of CS, resulting from the lack of widely available, standardized dosage form could be a reasonable explanation for the apparent discrepancy in the reports of clinical outcome after topical administration.

Medical devices in dermatology: topical semi-solid formulations for the treatment of skin diseases

In recent years, topically applied semi-solid formulations certified as medicals devices and not as topical drugs are increasingly used for the treatment of skin diseases. Medical devices primarily unfold their therapeutic effect by physical means, not by pharmacological, immunological or metabolic means. Intensified placing of medical devices on the dermatological market may at least partly be explained by a less complex marketing authorization process compared to topical drugs. If the requirements are fulfilled to certify a product as a medical device the opportunity will be offered to quickly introduce innovations onto the market and propagate them. A variety of evidence-based medical devices for several dermatological indications are presented here.

Antimicrobial Activity of Topical Formulations Containing Thymus vulgaris Essential Oil on Major Pathogens Causing Skin Diseases

The in vitro antimicrobial performance of topical semisolid formulations of the essential oil from Thymus vulgaris L. was assessed on major pathogenic microorganisms causing skin diseases. The essential oil wasobtained by hydrodistillation and formulated into five different semisolid vehicles. The inhibition zones of the active constituents released from their respective bases were determined by using agar well diffusionmethod. The formulations showed inhibition against the growth of microorganisms used in this study at a concentration of 1% (v/w). Bioactive compounds were released better from the hydrophilic preparationsthan from the hydrophobic ones. The release from macrogol blend was particularly better. The inhibition zone from macrogol blend against both the standard and clinical isolate of Pseudomonas aeruginosa was alsofound to be better than those of Fuciderm® cream (2% sodium fucidate) and tetracycline hydrochloride ointment (3% tetracycline).

HEDONIC AND DESCRIPTIVE SKINFEEL ANALYSIS OF TWO OLEOGELS: COMPARISON WITH OTHER TOPICAL FORMULATIONS

ABSTRACT Oleogels are gel systems obtained with an organogelator and a hydrophobic liquid. The sensory features and acceptance of one oleogel of cholesterol (3.5 wt %) and liquid paraffin and another of sorbitan monostearate (19 wt %) and sweet almond oil were evaluated along with other products representing four categories of topical semisolid formulations. In this study, differences between the two oleogels were observed on single attributes from the pickup and appearance categories, but principal component analysis demonstrated that they have similar overall sensory profiles. Both oleogels presented sensory properties that were closer to the W/O cream than to the other tested semisolid products. Related to the hedonic analysis, the oleogels were well appreciated by the consumers, which could lead to a positive impact on patient compliance. On the basis of their sensory features, we concluded that these oleogels could be promising vehicles for topical emollient formulations. PRACTICAL APPLICATIONSThe results of this work allowed the sensory characterization of novel semisolid formulations and the evaluation of their potential for application as dermatological bases or cosmetic products, considering the importance of sensory features on patient compliance. The methodology used was based on standard guidelines. Besides obtaining the sensory fingerprint of the two oleogels, which is important for guiding the optimization of the studied formulations, comparison between the sensory features of other topical formulations was achieved.

Comparison of a novel spray congealing procedure with emulsion-based methods for the micro-encapsulation of water-soluble drugs in low melting point triglycerides

The particle size characteristics and encapsulation efficiency of microparticles prepared using triglyceride materials and loaded with two model water-soluble drugs were evaluated. Two emulsification procedures based on o/w and w/o/w methodologies were compared to a novel spray congealing procedure. After extensive modification of both emulsification methods, encapsulation efficiencies of 13.04% tetracycline HCl and 11.27% lidocaine HCl were achievable in a Witepsol®-based microparticle. This compares to much improved encapsulation efficiencies close to 100% for the spray congealing method, which was shown to produce spherical particles of ∼58 μm. Drug release studies from a Witepsol® formulation loaded with lidocaine HCl showed a temperature-dependent release mechanism, which displayed diffusion-controlled kinetics at temperatures ∼25°C, but exhibited almost immediate release when triggered using temperatures close to that of skin. Therefore, such a system may find application in topical semi-solid formulations, where a temperature-induced burst release is preferred.

Investigation of the Utility of an In Vitro Release Test for Optimizing Semisolid Dosage Forms

Current literature indicates that an in vitro release test (IVRT) can serve as a research tool during the course of developing topical formulations. The purpose of this study was therefore to investigate the ability of an IVRT to select the topical semisolid formulations with the most rapid release rate of the model drug ketoprofen from two closely related hydrogels in a simulated product development process. Two glycols with distinct differences in their physical–chemical properties, Transcutol P (ethoxydiglycol) and propylene glycol, were incorporated into Carbopol 980 and Poloxamer 407 formulations. The release rate of ketoprofen was determined utilizing different receptor media and conditions, i.e., phosphate buffer pH 7.4, isopropyl myristate (IPM), and a combination of an IPM soaked membrane and phosphate buffer (pH 7.4) as receptor fluid. The results indicated that the conditions chosen could affect greatly the conclusions concerning the formulations. The only observable trend was that Transcutol P-containing formulations tended to permit a faster ketoprofen release than propylene glycol-containing formulations when utilizing IPM as a receptor component. This was attributed to the mutual miscibility of Transcutol P in IPM. It can be concluded that, for the purpose of formulation screening in the early phases of product development, an IVRT will only be useful for predicting the amount of drug available for absorption if the receptor medium has properties that closely mimic human skin. These results illustrate the importance of selecting suitable receptor components and indicate that it may be necessary to consider alternatives to the commonly used synthetic membranes.

Bioavailability assessment of topical delivery systems: in vitro delivery of minoxidil from prototypical semi-solid formulations

An in vitro technique has been developed for evaluating the delivery performance of topical semi-solid formulations. A thin and uniform layer of formulation was applied in facsimile to actual usage conditions by troweling the vehicle across a thin. circular copper template (200 μm in thickness). Approximately 30–45 mg of an oil-in-water cream, a water-in-oil cream or an ointment, each containing a range of concentrations of minoxidil, were applied over human cadaver skin within a defined circular area of 1.54 cm 2. The rates of permeation of minoxidil from these formulations were determined by finite dose diffusion experiments. For formulations containing 2% minoxidil, the flux from the w/o cream tested was about 4 times higher than fluxes from the o/w cream and the ointment. Even though all w/o formulations were initially saturated with drug, the flux of minoxidil from these creams increased as the concentration of minoxidil was increased from 0.5% to 2%. In contrast, the delivery rates from the o/w cream and the ointment did not appear to be dependent on the minoxidil concentration applied (0.5–2%). Under the operative experimental conditions, the percent coefficients of variation of flux of minoxidil from these formulations were less than 20%. To achieve this low level of variability, the skin samples were all obtained from the same cadaver abdomen. If one assumes that the efficacy of a particular formulation is dependent on the ability of the drug to be released from the vehicle and diffuse through the skin, the studies show that the nature of the vehicle can profoundly affect delivery even when excess solid drug is present. They also indicate that reliable in vitro comparisons of drug delivery are possible as long as one performs the studies on skin samples taken from the same section of skin.