A.

Latar Belakang
Tumbuhan tropis dunia diperkirakan lebih dari 250.000 spesies dan 1500 spesies
diantaranya merupakan family Sterculiaceae yang terdapat dalam 70 genus (Gressler,
dkk, 2007). Hasil penelusuran pustaka (Hakim 2008; Rohman 2005; Amrun dan Umiyah,
2005; Praptiwi 2006) diperoleh berbagai jenis tumbuhan sebagai sumber antioksidan
alami, satu di antaranya adalah dari suku Sterculiaceae.
Salah satu tumbuhan family Sterculiaceae yang tersebar di seluruh kepulauan
Indonesia dan sangat potensial untuk diteliti adalah Kleinhovia hospital Linn sebagai
tumbuhan yang berkhasiat (Imran,dkk, 2007). Secara tradisional, daun tumbuhan K.
hospita telah dimanfaatkan sebagai obat oleh masyarakat luas, khususnya di Sulawesi
Tenggara dan Selatan, dipercaya berkhasiat sebagai obat yang mampu mengobati
penyakit liver (Raflizar,2006).
Tumbuhan paliasa diyakini dapat menghasilkan senyawa-senyawa metabolit
sekunder yang memiliki bioaktivitas menarik dan efek terapetik yang ampuh. Secara
tradisional daun tumbuhan paliasa sudah dimanfaatkan sebagai obat tradisional secara
luas oleh masyarakat khususnya di Sulawesi Selatan dan dipercaya berkhasiat sebagai
obat yang mampu mengobati penyakit liver, hipertensi, dan diabetes (Dini dan Darminto,
2012). Di daerah Kalimantan Selatan, secara empirik daun paliasa dimanfaatkan oleh
masyarakat setempat untuk mencegah pertumbuhan uban (pemutihan warna) pada rambut
kepala dengan cara keramas. Akan tetapi, untuk pemanfaatan daun tersebut belum ada
kajian yang membuktikannya secara ilmiah.
Berbagai penelitian telah dilakukan bahwa kandungan kimia yang terdapat dalam
daun paliasa salah satunya adalah antioksidan. Saefudin dkk. (2013) telah melakukan

penelitian bahwa pada tumbuhan, K. hospita baik kulit batang maupun daunnya banyak
mengandung senyawa flavonoid. Flavonoid merupakan antioksidan yang kuat dan dapat
meredam radikal bebas, termasuk O2, H2O2, OH, dan singlet oksigen (O2) (Sakihama ,
2002). Selain itu, Kementrian Riset dan tekhnologi (2012) menjelaskan bahwa paliasa
diketahui mengandung senyawa aktif Eleutherol dan Kaempferol 3-glukosida yang
berfungsi sebagai zat antioksidan.
Antioksidan adalah senyawa yang berguna dalam membantu mengatasi kerusakan
oksidatif akibat radikal bebas atau senyawa oksigen reaktif. Antioksidan dapat bekerja
dengan cara mengatasi efek-efek kerusakan pada kulit manusia yang diakibatkan oleh
radikal bebas yang merupakan faktor utama pada proses penuaan (aging) dan kerusakan
jaringan kulit. Penuaan dini adalah proses penuaan kulit yang dapat terjadi akibat dari
paparan sinar matahari yang berlebihan. Sehingga, untuk memperlambat proses penuaan
kulit tersebut, kerusakan kulit perlu dicegah atau diperbaiki dengan menggunakan produk
kosmetik yang mengandung kolagen, vitamin, dan sebagainya. Salah satu bentuk sediaan
kosmetik yang sering digunakan yaitu sediaan krim (Amiruddin, 2003 ; Dirjen POM,
2005).
Krim adalah bentuk sediaan setengah padat berupa emulsi kental mengandung
tidak kurang dari 60% air, dimaksudkan untuk pemakaian luar. Tipe krim ini ada yang
bertipe air dalam minyak (A/M) dan minyak dalam air (M/A) (Anief, 1999).
Berdasarkan uraian diatas, telah dikatakan bahwa daun paliasa banyak
mengandung senyawa flavonoid. Oleh karena itu daun paliasa berpotensi untuk
dikembangkan menjadi sediaan krim antioksidan. Formulasi sediaan krim antioksidan
dari ekstrak etanol daun paliasa setelah diformulasikan kemudian diuji aktivitas
antioksidannya dengan menggunakan metode DPPH, serta pengujian stabilitas fisik

sediaan yang meliputi pengamatan organoleptik krim, uji pH, uji viskositas, dan
homogenitas serta uji stabilitas dengan metode sentrifugasi.
B. Rumusan Masalah
Berdasarkan latar belakang diatas, permasalahan yang dapat dikaji dalam penelitian
ini adalah :
1. Apakah ekstrak daun paliasa dapat diformulasikan menjadi sediaan krim?
2. Bagaimana stabilitas fisik formula sediaan krim ekstrak daun paliasa?
3. Bagaimana aktivitas antioksidan formulasi sediaan krim ekstrak daun paliasa?
C. Tujuan Penelitian
Tujuan dari penelitian ini adalah ;
1. Mendapatkan formulasi sediaan krim dari ekstrak daun paliasa
2. Mengetahui stabilitas fisik formula sediaan krim ekstrak daun paliasa
3. Mengetahui aktivitas antioksidan formulasi sediaan krim ekstrak daun paliasa
D. Manfaat Penelitian
Manfaat yang ingin dicapai dari penelitian ini adalah :
1. Menambah pengetahuan dan keterampilan bagi peneliti mengenai formulasi
sediaan krim khususnya dari bahan obat alam
2. Dapat di aplikasikan kepada masyarakat mengenai efek antioksidan dari formulasi
sediaan krim ekstrak daun paliasa
3. Dapat memberikan wawasan bagi peneliti-peneliti yang akan melakukan
penelitian lebih lanjut mengenai formulasi bahan obat alam
Menurut Halliwell dan Gutteridge (1989), radikal bebas adalah molekul atau
senyawa yang mempunyai satu atau lebih elektron yang tidak berpasangan dan dapat
menimbulkan kerusakan pada biomolekul. Senyawa antioksidan merupakan senyawa
yang memiliki manfaat salah satunya adalah mencegah penuaan dini.
Sistem tubuh manusia setiap saat terpapar radikal bebas baik yang dihasilkan dari
proses metabolisme normal maupun dari lingkungan, seperti asap rokok dan polusi.
Paparan radikal bebas yang berlebih terhadap tubuh dapat berakibat terhadap kerusakan
sel dan memicu patogenesis berbagai penyakit seperti penyakit kardiovaskular,
hipertensi, hiperlipidemia, diabetes, alzheimer, dan parkinson (Matteo dan Esposito,
2003; Touyz dan Schiffrin, 2004).

Indonesia merupakan Negara yang memiliki keanekaragaman hayati tumbuhan

tropis yang sangat potensial.
Sebagaimana diketahui, sekitar 1.260 jenis tumbuhan obat berasal dari hutan tropika Indonesia
(Zuhud ., 1994). Dari jumlah tersebut, beberapa di antaranya adalah tumbuhan endemik (Walujo,
2008). Hasil penelusuran pustaka (Hakim 2008; Rohman 2005; Amrun dan Umiyah, 2005;
Praptiwi 2006) diperoleh berbagai jenis tumbuhan sebagai sumber antioksidan alami, satu di
antaranya adalah dari suku Sterculiaceae.

Kerangka Konsep
Daun Ndokulo (Kleinhovia hospita L)

manfaatkan
enguap, asam
oleh
prusid
masyarakat
dan triterpenoid
luas sebagai
(Badan
bahan
POM,
obat
2006).
tradisional,
Paliasa khususnya
diketahui mengandung
penyakit liver,
senyawa
termasuk
aktd

Antioksidan

Formulasi sediaan Krim antioksidan ekstrak etanol daun paliasa (Kleinhovia hospita Linn)
sediaan Krim antioksidan ekstrak etanol daun paliasa (Kleinh

Evaluasi kestabilan krim meliputi:Uji aktivitas antioksidan

tidak lengket dan mudah dicuci denganorganoleptis
air. dibandingkan
dengan
salep, gel maupun pasta (W
viskositas,
pH,sediaan
dan homogenitas

rah tumbuh di kecamatan asera, kabupaten konawe utara

Daun

Tanaman paliasa

Ekstraksi
Ekstrak etanol daun paliasa

Formulasi krim

1%

2%

3%

Uji aktivitas antioksidan

Uji stabilitas
Organoleptis
Viskositas
pH
Inversi fase

Tetes dispersi
Volume kriming

Keterangan :
: Variabel bebas (diteliti)
: Variabel terikat (diteliti)
: Variabel antara (tidak diteliti)

Daun paliasa digunakan dan dipercaya berkhasiat sebagai obat yang mampu mengobati penyakit
liver, hipertensi, diabetes, kolesterol, dan hepatitis dengan cara meminum air rebusannya
(Herlina ;1993) dan Raflizar ; 2006)
Paliasa Tumbuhan ini mempunyai daun bertangkai panjang, berbentuk jantung lebar, dan
pada pangkalnya bertulang daun menjari. Selain itu, bunganya lebar dan berambut halus, serta
mempunyai 5 helai daun mahkota. Tumbuhan Katimaha kadang-kadang ditanam di bawah
ketinggian 500 m dari permukaan laut, terutama di tepi air dan tempat yang lembab. Sesuai
dengan tempat tumbuhnya, paliasa diberi nama yang berbeda-beda, misalnya di Madura dikenal
sebagai Mangar dan di daerah Sunda dikenal sebagai Katimaha (Steenis, 2003).
Secara umum Sterculiaceae memiliki karakteristik berupa pohon, semak, kadang-kadang
berupa liana dengan rambut-rambut bintang. Daunnya tunggal bertepi rata, kadang-kadang
berlekuk menjari atau majemuk, dan letaknya tersebar (Tjitrosoepomo, 2002). Pada bagian
bunganya terdapat 5 helai daun kelopak dan 5 helai daun mahkota (Steenis, 2003). Anggota
famili ini meliputi lebih dari 700 jenis yang tersebar di daerah tropika dan subtropika
(Tjitrosoepomo, 2002).
Paliasa merupakan daun segar atau telah dikeringkan. Tumbuhan Kleinhovia hospita L.
merupakan pohon dengan tinggi 5-20 meter. Daunnya bertangkai panjang, berbentuk jantung
dengan ukuran 4,5 x 27 cm x 3-2-24 cm; pada pangkal daun bertulang dan menjari.
Karakteristik: Daun paliasa berwarna hijau, berbau khas, rasa kelat. Habitat : Tanaman paliasa
tumbuh di dekat air, tanah basah atau lembab, tumbuh pada ketinggian 1- 1500 m di atas
pennukaan laut Tersebar diseluruh Indonesia Tumbuh khas di Sulawesi.
Mangar (Lampung, Madura), Tangkele (Sunda), Timaha (Jawa), kadanga (Flores), kayu
paliasa, Kauwasa, Katimaha (Makasar), Ayupali (Bugis), Ngaru (Temate).
Sedangkan di daerah Kalimantan Selatan, secara empirik daun Katimaha dimanfaatkan
oleh masyarakat setempat untuk mencegah pertumbuhan uban (pemutihan warna) pada rambut
kepala dengan cara keramas (Yunita, 2009).
Senyawa kaemferol dan kuersetin dapat berfungsi sebagai antitumor. Menurut Harjianti 2009,
pemicu tumor/kanker leukemia adalah efek dari radiasi dan pestisida, namun yang sering pula
dijumpai adalah efek dari hepatitis. Sementara virus hepatitis dapat dicegah atau pun
disembuhkan dengan mengkonsumsi ekstrak tumbuhan K. hospital (Raflizar,2006). Oleh karena
itu, secara empiris tumbuhan ini dapat digunakan sebagai obat hepatitis juga diduga sebagai
antitumor leukemia.
Saefudin dkk. (2013) telah melakukan penelitian bahwa pada tumbuhan, K. hospita baik kulit
batang maupun daunnya banyak mengandung senyawa flavonoid. Flavonoid merupakan
antioksidan yang kuat dan dapat meredam radikal bebas, termasuk O 2, H2O2, OH, dan singlet
oksigen (O2) (Sakihama , 2002).
Daun paliasa (Kleinhovia hospita L.) biasa digunakan sebagai obat tradisional untuk pengobatan
penyakit hati dan diabetes (Hasni, 2002).
Selain itu, tumbuhan ini sebelumnya telah ditemukan berkhasiat sebagai penurun kolesterol
tinggi, gula dan hipertensi, bahkan ekstrak daun tumbuhan ini dapat menyembuhkan pneumonia
dan iritasi mata (Latif, dkk., 1997).

KANDUNGAN KIMIA
Penelitian yang dilakukan oleh Waston dan Dalwit (2002), menemukan bahwa pada daun, kulit,
dan batang K. hospita diidentifikasi mengandung minyak atsiri, triterpenoid, sianogenin, asam
lemak dan siklopropenil. Khusus pada kayu batangnya ditemukan mengandung flavonol,
kaemferol dan kuersetin. Pawiroharsono (2003), menemukan bahwa senyawa kaemferol dan
kuersetin dapat berfungsi sebagai antikanker.
1.
2.
3.
4.
5.
6.
7.

tanaman
kulit
kosmetik
sinar matahari
uji aktivitas antioksidan
radikal bebas dan antioksidan
krim
a. komponen sediaan krim
1. Setil Alkohol 4 % b/b
Empirical Formula and Molecular Weight
C16H34O 242.44 (for pure material) Cetyl alcohol, used in pharmaceutical
preparations, is a mixture of solid aliphatic alcohols comprising mainly 1hexadecanol (C16H34O). The USP32NF27 specifies not less than 90.0% of
cetyl alcohol, the remainder consisting chiefly of related alcohols. Commercially,
many grades of cetyl alcohol are available as mixtures of cetyl alcohol (6070%)
and stearyl alcohol (2030%), the remainder being related alcohols.
Functional Category
Coating agent; emulsifying agent; stiffening agent.
Applications in Pharmaceutical Formulation or Technology
Cetyl alcohol is widely used in cosmetics and pharmaceutical formulations such
as suppositories, modified-release solid dosage forms, emulsions, lotions, creams,
and ointments. In suppositories cetyl alcohol is used to raise the melting point of
the base, and in modified-release dosage forms it may be used to form a
permeable barrier coating. In lotions, creams, and ointments cetyl alcohol is used
because of its emollient, water-absorptive, and emulsifying properties. It enhances
stability, improves texture, and increases consistency. The emollient properties are
due to absorption and retention of cetyl alcohol in the epidermis, where it
lubricates and softens the skin while imparting a characteristic velvety texture.
Cetyl alcohol is also used for its water absorption properties in water-in-oil

emulsions. For example, a mixture of petrolatum and cetyl alcohol (19 : 1) will
absorb 4050% of its weight of water. Cetyl alcohol acts as a weak emulsifier of
the water-in-oil type, thus allowing a reduction of the quantity of other
emulsifying agents used in a formulation. Cetyl alcohol has also been reported to
increase the consistency of water-in-oil emulsions.
In oil-in-water emulsions, cetyl alcohol is reported to improve stability by
combining with the water-soluble emulsifying agent. The combined mixed
emulsifier produces a close packed, monomolecular barrier at the oilwater
interface which forms a mechanical barrier against droplet coalescence.
In semisolid emulsions, excess cetyl alcohol combines with the aqueous
emulsifier solution to form a viscoelastic continuous phase that imparts semisolid
properties to the emulsion and also prevents droplet coalescence. Therefore, cetyl
alcohol is sometimes referred to as a consistency improver or a bodying agent,
although it may be necessary to mix cetyl alcohol with a hydrophilic emulsifier to
impart this property.
It should be noted that pure or pharmacopeial grades of cetyl alcohol may
not form stable semisolid emulsions and may not show the same physical
properties as grades of cetyl alcohol that contain significant amounts of other
similar alcohols.
Table I: Uses of cetyl alcohol.
Use Concentration (%)
Emollient

25

Emulsifying agent

25

Stiffening agent

210

Water absorption

Description
Cetyl alcohol occurs as waxy, white flakes, granules, cubes, or castings. It has a
faint characteristic odor and bland taste.

Stability and Storage Conditions

Cetyl alcohol is stable in the presence of acids, alkalis, light, and air; it does not
become rancid. It should be stored in a well-closed container in a cool, dry place.
Incompatibilities
Incompatible with strong oxidizing agents. Cetyl alcohol is responsible for
lowering the melting point of ibuprofen, which results in sticking tendencies
during the process of film coating ibuprofen crystals.
Method of Manufacture
Cetyl alcohol may be manufactured by a number of methods such as esterification
and hydrogenolysis of fatty acids or by catalytic hydrogenation of the
triglycerides obtained from coconut oil or tallow. Cetyl alcohol may be purified
by crystallization and distillation.
Safety
Cetyl alcohol is mainly used in topical formulations, although it has also been
used in oral and rectal preparations. Cetyl alcohol has been associated with
allergic delayed-type hypersensitivity reactions in patients with stasis dermatitis.
(2) Crosssensitization with cetostearyl alcohol, lanolin, and stearyl alcohol has
also been reported.(3,4) It has been suggested that hypersensitivity may be caused
by impurities in commercial grades of cetyl alcohol since highly refined cetyl
alcohol (99.5%) has not been associated with hypersensitivity reactions.(5)
2. gliserin 15 % b/v
Synonyms
Croderol; E422; glicerol; glycerine; glycerolum; Glycon G-100; Kemstrene;
Optim; Pricerine; 1,2,3-propanetriol; trihydroxypropane glycerol.
Chemical Name and CAS Registry Number
Propane-1,2,3-triol [56-81-5] 4 Empirical Formula and Molecular Weight
C3H8O3 92.09
Structural Formula

Functional Category

Antimicrobial preservative; cosolvent; emollient; humectant; plasticizer; solvent;

sweetening agent; tonicity agent.
Applications in Pharmaceutical Formulation or Technology
Glycerin is used in a wide variety of pharmaceutical formulations
including oral, otic, ophthalmic, topical, and parenteral preparations; see Table I.
In topical pharmaceutical formulations and cosmetics, glycerin is used
primarily for its humectant and emollient properties. Glycerin is used as a solvent
or cosolvent in creams and emulsions.(13) Glycerin is additionally used in
aqueous and nonaqueous gels and also as an additive in patch applications.(46)
In parenteral formulations, glycerin is used mainly as a solvent and cosolvent.(7
10)
In oral solutions, glycerin is used as a solvent,(10) sweetening agent,
antimicrobial preservative, and viscosity-increasing agent. It is also used as a
plasticizer and in film coatings.(1114)
Glycerin is used as a plasticizer of gelatin in the production of soft-gelatin
capsules and gelatin suppositories.
Glycerin is employed as a therapeutic agent in a variety of clinical
applications,(15) and is also used as a food additive.

Description
Glycerin is a clear,
colorless, odorless, viscous, hygroscopic liquid; it has a sweet taste,
approximately 0.6 times as sweet as sucrose.
Stability and Storage Conditions
Glycerin is hygroscopic. Pure glycerin is not prone to oxidation by the
atmosphere under ordinary storage conditions, but it decomposes on heating with
the evolution of toxic acrolein. Mixtures of glycerin with water, ethanol (95%),
and propylene glycol are chemically stable.

Incompatibilities
Glycerin may explode if mixed with strong oxidizing agents such as
chromium trioxide, potassium chlorate, or potassium permanganate. In dilute
solution, the reaction proceeds at a slower rate with several oxidation products
being formed. Black discoloration of glycerin occurs in the presence of light, or
on contact with zinc oxide or basic bismuth nitrate.
An iron contaminant in glycerin is responsible for the darkening in color
of mixtures containing phenols, salicylates, and tannin.
Glycerin forms a boric acid complex, glyceroboric acid, that is a stronger
acid than boric acid.
3. TEA % b/v (2,3,4)
Synonyms
TEA; Tealan; triethylolamine; trihydroxytriethylamine; tris (hydroxyethyl)amine;
trolaminum.
Chemical Names and CAS Registry Number
2,20,200-Nitrilotriethanol [102-71-6]
Empirical Formula and Molecular Weight
C6H15NO3 149.19
Structural Formula

Functional Category
Alkalizing agent; emulsifying agent.
Applications in Pharmaceutical Formulation or Technology
Triethanolamine is widely used in topical pharmaceutical formulations,
primarily in the formation of emulsions.

When mixed in equimolar proportions with a fatty acid, such as stearic

acid or oleic acid, triethanolamine forms an anionic soap with a pH of about 8,
which may be used as an emulsifying agent to produce fine-grained, stable oil-inwater emulsions. Concentrations that are typically used for emulsification are 2
4% v/v of triethanolamine and 25 times that of fatty acids. In the case of mineral
oils, 5% v/v of triethanolamine will be needed, with an appropriate increase in the
amount of fatty acid used. Preparations that contain triethanolamine soaps tend to
darken on storage. However, discoloration may be reduced by avoiding exposure
to light and contact with metals and metal ions.
Triethanolamine is also used in salt formation for injectable solutions and
in topical analgesic preparations. It is also used in sun screen preparations.(1)
Triethanolamine is used as an intermediate in the manufacturing of
surfactants,

textile

specialties,

waxes,

polishes,

herbicides,

petroleum

demulsifiers, toilet goods, cement additives, and cutting oils. Triethanolamine is

also claimed to be used for the production of lubricants for the rubber gloves and
textile industries. Other general uses are as buffers, solvents, and polymer
plasticizers, and as a humectant.
Description
Triethanolamine is a clear, colorless to pale yellow-colored viscous liquid
having a slight ammoniacal odor. It is a mixture of bases, mainly 2,20,200nitrilotriethanol, although it also contains 2,20- iminobisethanol (diethanolamine)
and smaller amounts of 2- aminoethanol (monoethanolamine).
Stability and Storage Conditions
Triethanolamine may turn brown on exposure to air and light.
The 85% grade of triethanolamine tends to stratify below 158C;
homegeneity can be restored by warming and mixing before use.
Triethanolamine should be stored in an airtight container
protected from light, in a cool, dry place.
Incompatibilities
Triethanolamine is a tertiary amine that contains hydroxy groups; it is
capable of undergoing reactions typical of tertiary amines and

alcohols.

Triethanolamine will react with mineral acids to form crystalline salts and esters.

With the higher fatty acids, triethanolamine forms salts that are soluble in water
and have characteristics of soaps. Triethanolamine will also react with copper to
form complex salts. Discoloration and precipitation can take place in the presence
of heavy metal salts.
Triethanolamine can react with reagents such as thionyl chloride to replace
the hydroxy groups with halogens. The products of these reactions are very toxic,
resembling other nitrogen mustards.
4. asam stearat % b/b (6,12,18)
Synonyms
Acidum stearicum; cetylacetic acid; Crodacid; Cristal G; Cristal S; Dervacid;
E570; Edenor; Emersol; Extra AS; Extra P; Extra S; Extra ST; 1heptadecanecarboxylic acid; Hystrene; Industrene; Kortacid 1895; Pearl Steric;
Pristerene; stereophanic acid; Tegostearic.
Chemical Name and CAS Registry Number
Octadecanoic acid [57-11-4]
Empirical Formula and Molecular Weight
C18H36O2 284.47 (for pure material) The USP32NF27 describes stearic acid as
a mixture of stearic acid (C18H36O2) and palmitic acid (C16H32O2). In the
USP32 NF27, the content of stearic acid is not less than 40.0% and the sum of
the two acids is not less than 90.0%. The USP32NF27 also contains a
monograph for purified stearic acid; see Section 17. The PhEur 6.5 contains a
single monograph for stearic acid but defines stearic acid 50, stearic acid 70, and
stearic acid 95 as containing specific amounts of stearic acid (C18H36O2); see
Section 9.
Structural Formula

Functional Category
Emulsifying agent; solubilizing agent; tablet and capsule lubricant.
Applications in Pharmaceutical Formulation or Technology
Stearic acid is widely used in oral and topical pharmaceutical
formulations. It is mainly used in oral formulations as a tablet and capsule
lubricant;(13) see Table I, although it may also be used as a binder(4) or in

combination with shellac as a tablet coating. It has also been suggested that stearic
acid may be used in enteric tablet coatings and as a sustained-release drug carrier.
(5)
In topical formulations, stearic acid is used as an emulsifying and
solubilizing agent. When partially neutralized with alkalis or triethanolamine,
stearic acid is used in the preparation of creams.(6,7) The partially neutralized
stearic acid forms a creamy base when mixed with 515 times its own weight of
aqueous liquid, the appearance and plasticity of the cream being determined by
the proportion of alkali used.
Stearic acid is used as the hardening agent in glycerin suppositories.
Stearic acid is also widely used in cosmetics and food products.

Description
Stearic acid is a hard, white or faintly yellow-colored, somewhat glossy,
crystalline solid or a white or yellowish white powder. It has a slight odor (with an
odor threshold of 20 ppm) and taste suggesting tallow.
Stability and Storage Conditions
Stearic acid is a stable material; an antioxidant may also be added to it.
The bulk material should be stored in a wellclosed container in a cool, dry place.
Incompatibilities
Stearic acid is incompatible with most metal hydroxides and may be
incompatible with bases, reducing agents, and oxidizing agents.
Ointment bases made with stearic acid may show evidence of drying out
or lumpiness due to such a reaction when compounded with zinc or calcium salts.
A number of differential scanning calorimetry studies have investigated
the compatibility of stearic acid with drugs. Although such laboratory studies have
suggested incompatibilities, e.g. with naproxen,(9) they may not necessarily be
applicable to formulated products.

Stearic acid has been reported to cause pitting in the film coating of tablets
applied using an aqueous film-coating technique; the pitting was found to be a
function of the melting point of the stearic acid.(10)
5. metil paraben % b/b (0,2)
Synonyms
Aseptoform M; CoSept M; E218; 4-hydroxybenzoic acid methyl ester; metagin;
Methyl Chemosept; methylis parahydroxybenzoas; methyl p-hydroxybenzoate;
Methyl Parasept; Nipagin M; Solbrol M; Tegosept M; Uniphen P-23.
Chemical Name and CAS Registry Number
Methyl-4-hydroxybenzoate [99-76-3]
Empirical Formula and Molecular Weight
C8H8O3 152.15
Structural Formula

Functional Category
Antimicrobial preservative.
Applications in Pharmaceutical Formulation or Technology
Methyl paraben is widely used as an antimicrobial preservative in
cosmetics, food products, and pharmaceutical formulations; see Table I. It may be
used either alone or in combination with other parabens or with other
antimicrobial agents. In cosmetics, methylparaben is the most frequently used
antimicrobial preservative.(1)
The parabens are effective over a wide pH range and have a broad
spectrum of antimicrobial activity, although they are most effective against yeasts
and molds. Antimicrobial activity increases as the chain length of the alkyl moiety
is increased, but aqueous solubility decreases; therefore a mixture of parabens is
frequently used to provide effective preservation. Preservative efficacy is also

improved by the addition of propylene glycol (25%), or by using parabens in

combination with other antimicrobial agents such as imidurea; see Section 10.
Owing to the poor solubility of the parabens, paraben salts (particularly
the sodium salt) are more frequently used in formulations. However, this raises
the pH of poorly buffered formulations.
Methylparaben (0.18%) together with propylparaben (0.02%) has been
used for the preservation of various parenteral pharmaceutical formulations; see
Section 14.
Description
Methylparaben occurs as colorless crystals or a white crystalline powder.
It is odorless or almost odorless and has a slight burning taste.
Stability and Storage Conditions
Aqueous solutions of methylparaben at pH 36 may be sterilized by
autoclaving at 1208C for 20 minutes, without decomposition.(8) Aqueous
solutions at pH 36 are stable (less than 10% decomposition) for up to about 4
years at room temperature, while aqueous solutions at pH 8 or above are subject
to rapid hydrolysis (10% or more after about 60 days storage at room
temperature).
Methylparaben should be stored in a well-closed container in a cool, dry
place.
Incompatibilities
The antimicrobial activity of methylparaben and other parabens is
considerably reduced in the presence of nonionic surfactants, such as polysorbate
80, as a result of micellization.(10,11) However, propylene glycol (10%) has been
shown to potentiate the antimicrobial activity of the parabens in the presence of
nonionic surfactants and prevents the interaction between methylparaben and
polysorbate 80.(12)
Incompatibilities with other substances, such as bentonite,(13) magnesium
trisilicate,(14) talc, tragacanth,(15) sodium alginate,(16) essential oils,(17)
sorbitol,(18) and atropine,(19) have been reported. It also reacts with various
sugars and related sugar alcohols.(20)

Absorption of methylparaben by plastics has also been reported; the

amount absorbed is dependent upon the type of plastic and the vehicle. It has been
claimed that low-density and high-density polyethylene bottles do not absorb
methylparaben.(21)
Methylparaben is discolored in the presence of iron and is subject to
hydrolysis by weak alkalis and strong acids.
6. propil paraben % b/b (0,02)
Synonyms
Aseptoform P; CoSept P; E216; 4-hydroxybenzoic acid propyl ester; Nipagin P;
Nipasol M; propagin; Propyl Aseptoform; propyl butex; Propyl Chemosept;
propylis parahydroxybenzoas; propyl phydroxybenzoate; Propyl Parasept; Solbrol
P; Tegosept P; Uniphen P-23.
Chemical Name and CAS Registry Number
Propyl 4-hydroxybenzoate [94-13-3]
Empirical Formula and Molecular Weight
C10H12O3 180.20
Structural Formula

Applications in Pharmaceutical Formulation or Technology

Propylparaben is widely used as an antimicrobial preservative in
cosmetics, food products, and pharmaceutical formulations; see Table I.
It may be used alone, in combination with other paraben esters, or with
other antimicrobial agents. It is one of the most frequently used preservatives in
cosmetics.(1)
The parabens are effective over a wide pH range and have a broad
spectrum of antimicrobial activity, although they are most effective against yeasts
and molds; see Section 10.
Owing to the poor solubility of the parabens, the paraben salts, particularly
the sodium salt, are frequently used in formulations. This may cause the pH of
poorly buffered formulations to become more alkaline.
Propylparaben (0.02% w/v) together with methylparaben (0.18% w/v) has
been used for the preservation of various parenteral pharmaceutical formulations;

See Methylparaben for further information.

Description
Propylparaben occurs as a white, crystalline, odorless, and tasteless
powder.
Stability and Storage Conditions
Aqueous propylparaben solutions at pH 36 can be sterilized by
autoclaving, without decomposition.(4) At pH 36, aqueous solutions are stable
(less than 10% decomposition) for up to about 4 years at room temperature, while
solutions at pH 8 or above are subject to rapid hydrolysis (10% or more after
about 60 days at room temperature).(5)
Incompatibilities
The antimicrobial activity of propylparaben is reduced considerably in the
presence of nonionic surfactants as a result of micellization.(6) Absorption of
propylparaben by plastics has been reported, with the amount absorbed dependent
upon the type of plastic and the vehicle.(7) Magnesium aluminum silicate,
magnesium trisilicate, yellow iron oxide, and ultramarine blue have also been
reported to absorb propylparaben, thereby reducing preservative efficacy.(8,9)
Propylparaben is discolored in the presence of iron and is subject to
hydrolysis by weak alkalis and strong acids. See also Methylparaben.
7. pengaroma (2 tetes)

2. Evaluasi Krim (28, 32, 33)

a. Pengamatan Organoleptis
Diamati perubahan warna, bau (ketengikan), dan terjadinya pemisahan fase.
b. Pengamatan Homogenitas
Mengamati ukuran partikel-partikel pada kaca objek, untuk mengetahui terbentuk partikelpartikel kasar.
c. Pemeriksaan pH
Pengukuran pH dilakukan dengan menggunakan pH meter yang telah dikalibrasi dengan
menggunakan larutan dapar standar pH 4 dan 7. Pengukuran pada sediaan krim dilakukan
pada suhu kamar.
d. Pengamatan diameter globul rata-rata
Pengukuran globul rata-rata dilakukan dengan menggunakan mikroskop optik, krim
diletakkan di atas kaca objek dan ditutup dengan gelas penutup kemudian dengan
menggunakan haemasitometer dan mikroskop pada perbesaran tertentu. Kemudian foto
gambar yang diamati dengan menggunakan kamera digital dan ukur diameter partikelnya
dan distribusi partikelnya.
Metode Cycling test
Sampel krim disimpan pada suhu 4oC selama 24 jam lalu pindahkan ke dalam oven yang
bersuhu 40+2oC selama 24 jam (satu siklus), kemudian uji dilakukan sebanyak 6 siklus
kemudian diamati terjadi adanya pemisahan fase.
Uji Mekanik (Sentrifugasi)
Sampel krim dimasukkan ke dalam alat sentrifugasi kemudian dimasukkan ke dalam alat
sentrifugator pada kecepatan 3750 rpm selama 5 jam atau 5000-10.000 rpm selama 30 menit.

Perlakuan tersebut sama dengan perlakuan adanya gaya gravitasi selama setahun. Kemudian
diamati apakah terjadi pemisahan atau tidak.