The Study Regarding the Formulation, Preparation, and Control of some Uncoated Tablets with Nootropic Action

FIȚA Cătălina Ancuța1*, LUPULIASA Dumitru1, OZON Emma Adriana1, BALACI Teodora Dalila1

1 Pharmaceutical Technology Department, Faculty of Pharmacy, ”Carol Davila” University of Medicine and Pharmacy, 6, Traian Vuia Street, 020956, Bucharest (ROMANIA)

*corresponding author,


Memory disorders represent a group of complex neurodegenerative dysfunctions, of various etiologies, having as a common symptom the diminution or even loss of the ability to memorize, in the short or long term. This experimental work aimed to develop a dosage form for oral administration, effective in the adjuvant treatment of neural disorders such as memory, attention, and concentration impairments, both by specific action against these deficiencies and neuroprotection or decreased oxidative stress. The product resulted from the association of some processed vegetable components in the dosage form some of the vegetable extracts (Ginkgo biloba L, Bacopa monnieri L., Melissa officinalis L.), a powder of an herb (Cеntеlla asiatica L.) brought to a corresponding degree of fineness and a tincture (Rosmarinus officinalis L). The tablets were prepared by direct compression, using appropriate diluents, binders and disintegrants characteristic of this method, such as lactose monohydrate (Exciprеss ™ SD2) were chosen as the diluent excipient, microcrystalline cellulose (Avicеl PH 101) and polyvinylpyrrolidone (PVP K®) as binder excipients, the magnesium stearate and talc as lubricants and disintegrants. Direct compression has become an increasingly used method in the pharmaceutical industry, due to its many advantages. During production, after production, and during conservation, tablets were tested to determine: organoleptic characteristics, mass uniformity, hardness, friability, and disintegration, the results being within the admissible limits of actual normative. The proposed formula resulted in a pharmaceutically suitable preparation.

Keywords: vegetal extract, tincture, directly compressible excipient, nootropic tablet.


At the level of the nervous system, neurodegenerative disorders are initially manifested by minor symptoms, often imperceptible to memory and cognitive ability, which evolve with behavioral changes and gradual reduction of simple and complex neuronal functions: motivations, emotions, language. The best known neurodegenerative diseases that affect memory are: dementia, Alzheimer`s disease, vascular dementia, Parkinson`s disease.

Nootropics (cognitive enhancers) are drugs, supplements, and other substances that may improve cognitive function, particularly executive functions, memory, creativity, or motivation, in healthy individuals. These products act through several mechanisms and perform cholinesterase and secretase inhibitory activities, have anti-inflammatory and antioxidant or metal chelating effects [1, 2, 3, 4].

The objective of this study was to formulate and prepare some tablets with dry vegetal extracts. After consulting the specialty literature, we selected several vegetal products which act as cognitive enhancers, having antioxidant, tonic, CNS stimulating action and much more, with beneficial effects on memory and attention disorders [5, 6]:

Ginkgo biloba extract is a cognitive enhancer who improve memory loss associated with blood circulation abnormality, has neuroprotective properties due to flavonoids-kaemferol, quercetin – which have antioxidant activity. Ginkgolides (A, B, C, J, and M) improves blood circulation and bilobalide (sesquiterpenes trilactone) can reduce damage caused by brain ischemia [7];Centella asiatica leaf extract, known as Gotu Kola is an ancient Ayurvedic remedy used to strengthen nerve function and memory, to improve learning memory (through the monoterpenes present in the essential oil: α-pinene, β-pinene, bornyl acetyl acetate inhibits the action of the enzyme acetylcholine esterase (AChE) [8-11];
Bacopa monnieri, known as Brahmi, is an Ayurvedic medicinal plant used as a nerve tonic. It has antioxidant, cholinesterase inhibitory, and anti-inflammatory action given by saponins (Bacoside A, Bacoside B) the main active ingredients but also by flavonoids (apigenin), glycosides (asiaticoside) and alkaloids (brahmin) [12];
Rosmarinus officinalis L, methanolic extract, has the highest inhibitory activity against AChE due to the components of essential oil: 1-8 cineol, α-pinene (terpenoids compounds) and rosmarinic acid (a phenolic compound) [11-15];
Melissa officinalis L extract is used as a calming and strengthening remedy and to treat migraines, promoting long life and for memory recovery. It is useful in dementia with antioxidant effects (essential oil-monoterpenes: citral, geraniol).
To facilitate the compression process, a mixture of diluents-binders-disintegrants-lubricants-glidants, directly compressible (DC) was used. The good compressibility properties of the excipients: the good flow, adhesiveness, and density of the powders facilitated the obtaining of the tablets by the method of direct compression [16-18].

Materials and methods
The following materials were used:
Active components:
– dry standardized extract from Ginko Biloba L. (Ginkgoaceae) leaf, powder;
– dry extract from Mеlissa Officinalis L (Lamiaceae), Lemon balm, powder;
– dry standardized extract from Bacopa monniеri L. (Scrophulariaceae), Brahmi, powder;
– Cеntеlla asiatica (Umbelliferae) L., Gotu kola, powder;
– Rosmarinus officinalis L.(Lamiaceae), Rosemary, tincture;

Auxiliary components (Excipients):
– lactose monohydrate – Еxciprеss™ SD2;
– microcrystalline cellulose-Avicеl PH®101;
– polyvinylpyrrolidone-PVP K®;
– Talcum powder;
– Magnesium stearate, powder.

Formulation and obtaining the nootropic tablets

Table I – The formula of the tablet with the nootropic action

Components mg/tablet Role/Action
Ginkgo Biloba extract, powder 70 Active/Nootropic
Bacopa monniеri extract, powder 120 Nootropic
Cеntеlla asiatica, powder 100 Nootropic
Mеlissa officinalis extract, powder 100 Nootropic
Rosmarinus officinalis, tincture 1 Nootropic
Lactose monohydrate (Еxciprеss™ SD2) 190 Filler
Microcrystalline cellulose (Avicеl PH ®101) 190 Binder
Polyvinylpyrrolidone (PVP K®) 17,27 Binder
Talcum 3,72 Glidant
Magnesium stearate 8,13 Lubricant./disintegrant
Total 800


  The excipients of the formula (Table 1), were powdered, sieved through a 0,8 mm mesh sieve and mix for 15 minutes until a uniform powder is obtained. Separately, the powder mixture and vegetable extract are obtained in the same way. The mixture of active vegetal principles is brought to the excipients and the mixture is homogenized, grinding for mixing and homogenization for 15 minutes. After obtaining a homogeneous mixture, incorporate the rosemary tincture added in drops and mix to avoid agglomeration of the particles; repeat this step until the prescribed amount of tincture is exhausted. The mixture obtained is again grounded for homogenization and uniformization. Determination of the homogeneity of the powder mixture used to obtain the tablets 

For the obtained composite powder the flow properties were studied:

  • Apparent densities before and after tapped powder, compression behavior (Vankel Tap Dеnsity® Apparatus);
  • The compressibility index and the Haussner ratio (applying formulas provided in the literature);
  • Moisture content (HR 73 Mettler Toledo halogen moisture analyzer).

The lubricants were sieved through a 600-mesh sieve, added to the mixture and further mixed for 5 minutes. The final mixture was then compressed using a Korsch EK-O type press, to produce 800 mg tablets. The dies/punches set were 13 mm wide, with flat faces. 

Quality control of nootropic  tablets

The tablets were analyzed after preparation and after 6 and 12 months, the following determinations being performed: the determination of the organoleptic characteristics, mass uniformity, mechanical resistance, friability, and disintegration.

The equipment used for these determinations was:

  • for the determination of mass uniformity: Mettler Toledo balance and the method described in the Romanian`s Pharmacopoeia, X th. edition;
  • for the determination of the hardness and height: the Vanderkampf VK 200 tester 

and the method described in the Eur. Ph. 8th edition [19];

  • for the determination of the friability: VanKel friabilator and the method described in the Eur. Ph. 8th edition [19];
  • for the determination of the disintegration time: Sotax DT3 apparatus and method A described in the Romanian`s Pharmacopoeia, X th edition.

Results and Discussion

The blend was evaluated for the parameters such as the angle of repose, bulk density, tapped density, compressibility index, Hausner’s ratio, and moisture content.

Table II– Pre-compression parameter for formulation (Mean±SD, n=3)

Property Formula
The angle of response (Θ)  42.8±0.03
Bulk density (g/cm3) 0.447±0.02
Tapped density (g/cm3) 0.625±0.01
Haussner ratio 1.39±0.12
Carr index % 29.48%±0.21
Moisture content (%) 1,70±0.04

The results of micromeritics properties (Table 2) were found to be within satisfactory limits.

The tablets obtained from the compression of the analyzed compound powder had the following characteristics:

  • Aspеct: non-coated tablets with compact structure, disc-shaped, with intact edges, smooth surface, flat and diameter dе 13.1 mm and height dе 4.7 mm;
  • Color: beige color tablet, with brown pigments, homogeneously distributed; 
  • Odor-characteristic of the mixture of vegetable powders;
  • Bitter taste due to the bitter principles contained in the vegetal, characteristic products.
  • The variation of the individual mass of the uncoated tablets:

Figure 1– The variation of the individual mass and  the percentage 

deviation of the uncoated tablets

These uncoated tablets correspond in terms of individual mass, the mass limits in which the mass of the tablets may vary are 0.7619-0.8421 g, and the percentage deviation varies between -1,5 si 2,24.

The data obtained after the evaluation of pharmacotechnical factors of nootropic tablets after preparation and after 6 and 12 months are depicted in Table III.

Table III– Pharmacotehnical factors of tablets (Mean±SD, n=3)

Parameters After preparation After 6 month After 12 month
Height (mm) 4.71±0.012 4.71±0.01 4.71±0.01
Diameter (mm) 13.1±0.021 13.1±0.02 13.1±0.02
Hardness (Kp) 9.54±0.031 9.23±0.01 9.23±0.01
Friability (%) 0 0.2±0.01 0..2±0.01

The mechanical resistance of the tablets is good and the friability is very good. After 6 and 12 months of preservation, the values for the tablet characteristics have shown insignificant variations.

Disintegration: For the test, 6 uncoated tablets were used at the same time, under the same conditions, so that all samples were introduced into the same water baths maintained at 36-38 °C.[9]

Figure 2 – Disintegration diagram of uncoated tablets

The uncoated tablets with nootropic action correspond to the official norms for disintegration, the interval being between 13.43 – 15 minutes.


The use of the direct compression method for the production of tablets ensures the stability of the vegetals components. Also, some carefully selected, directly compressible excipients were used, which helped maintain the action of the active ingredients and produce tablets with adequate stability. The nootropic action of these tablets is expected to be considered because the tablets contain various natural compounds (in the form of extracts, powder, and tincture) in adequate concentrations.

These tablets can be a starting point in obtaining industrial preparations that can be used as a dietary supplement for lifestyle improvement and as an adjunct in the treatment of attention and concentration disorders.


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